Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “mitochondrial dysfunction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,693 records · Page 94Linked to original sources
PubMed1985

The effect of Coenzyme Q10 on reperfusion injury in canine myocardium.

The mechanism of mitochondrial damage during reperfusion injury of ischemic myocardium was studied using mongrel dogs in vivo and isolated mitochondria in vitro. Seventy-seven adult dogs were divided into three groups: the control group (n = 38), the Coenzyme Q10 (CoQ10)-5 mg group (n = 24), and the CoQ10-15 mg group (n = 15). In the control group, the left anterior descending coronary artery (LAD) of the dog was occluded for 15 min followed by 5 min of reperfusion after 40 min of premedication with physiological saline. In both CoQ10 groups, 5 mg/kg or 15 mg/kg of CoQ10 was infused intravenously for 20 min and then physiological saline was administered for 20 min before 15 min occlusion of the LAD. Subsequently, reperfusion was allowed for 5 min. Each group was further divided into two subgroups depending on the presence (arrhythmia group) or the absence (non-arrhythmia group) of ventricular arrhythmias. Immediately after 15 min occlusion, myocardial samples were taken from the normal and reperfused areas to measure CoQ10 content of myocardium. Heart mitochondria were prepared after 5 min of reperfusion from both areas. Arrhythmias appeared in 12 of 38 dogs in the control group (32%), two of 24 dogs in the CoQ10-5 mg group (8%) and none of 15 dogs in the CoQ10-15 mg group (0%). Premedication with CoQ10 increased tissue CoQ10 content in a dose-dependent manner. In the CoQ10-5 mg group, the increase in CoQ10 content of dogs with reperfusion arrhythmias was relatively less than that of dogs without reperfusion arrhythmias. In each group, mitochondrial function was decreased in the arrhythmia group compared to that of the non-arrhythmia group. The increase in free fatty acid (FFA) content and the decrease in phospholipid content were also observed in mitochondria from the reperfused area of each arrhythmia group. The increase in FFA and mitochondrial dysfunction were induced by the incubation of mitochondria in vitro with phospholipase (PLase) A2 or PLase C, and protected by the addition of CoQ10. These results suggest that PLase plays an important role in the development of mitochondrial damage associated with reperfusion.

Animals↗
PubMed2004

Mitochondrial injury in steatohepatitis.

Rich diet and lack of exercise are causing a surge in obesity, insulin resistance and steatosis, which can evolve into steatohepatitis. Patients with non-alcoholic steatohepatitis have increased lipid peroxidation, increased tumour necrosis factor-alpha (TNF-alpha) and increased mitochondrial beta-oxidation rates. Their in-vivo ability to re-synthesize ATP after a fructose challenge is decreased, and their hepatic mitochondria exhibit ultrastructural lesions, depletion of mitochondrial DNA and decreased activity of respiratory chain complexes. Although the mechanisms for these effects is unknown, the basal cellular formation of reactive oxygen species (ROS) may oxidize fat deposits to cause lipid peroxidation, which damages mitochondrial DNA, proteins and cardiolipin to partially hamper the flow of electrons within the respiratory chain. This flow may be further decreased by TNF-alpha, which can release cytochrome c from mitochondria. Concomitantly, the increased mitochondrial fatty acid beta-oxidation rate augments the delivery of electrons to the respiratory chain. Due to the imbalance between a high electron input and a restricted outflow, electrons may accumulate within complexes I and III, and react with oxygen to form the superoxide anion radical. Increased mitochondrial ROS formation could in turn directly oxidize mitochondrial DNA, proteins and lipids, enhance lipid peroxidation-related mitochondrial damage, trigger hepatic TNF-alpha formation and deplete antioxidants, thus further blocking electron flow and further increasing mitochondrial ROS formation. Mitochondrial dysfunction plays an important role in liver lesions, through the ROS-induced release of both biologically active lipid peroxidation products and cytokines. In particular, the up-regulation of both TNF-alpha and Fas triggers mitochondrial membrane permeability and apoptosis. The ingestion of apoptotic bodies by stellate cells stimulates fibrogenesis, which is further activated by lipid peroxidation products and high leptin levels. Chronic apoptosis is compensated by increased cell proliferation, which, together with oxidative DNA damage, may cause gene mutations and cancer.

Adipocytes↗
PubMed1989

Screening for mitochondrial cytopathies: the sub-anaerobic threshold exercise test (SATET).

A simple test is described for identifying patients with abnormalities of muscle energy metabolism secondary to mitochondrial dysfunction, based on the venous lactate response to exercise at 90% of predicted work rate at the anaerobic threshold. The test was standardised for age, weight and sex of subjects, and was abnormal in all cases of mitochondrial cytopathy tested, with a false positive rate of 7% in a control population. The test was abnormal in two cases of mitochondrial disease in which muscle biopsy was normal or showed only non-specific changes.

Adult↗
PubMed2004

Hyperlactatemia in human immunodeficiency virus-uninfected infants who are exposed to antiretrovirals.

OBJECTIVE: Exposure to nucleoside analogues in fetal or early life has been associated with rare clinically significant mitochondrial toxic effects, mainly neurologic symptoms. Lactate (LA) measurements have been used to monitor nucleoside-related mitochondrial toxicity. Our aim was to determine the prevalence, clinical evolution, and risk factors for hyperlactatemia in our cohort of human immunodeficiency virus (HIV)-uninfected children who were exposed to antiretrovirals. METHODS: We conducted a prospective observational study of 127 HIV-uninfected infants who were born to HIV-infected women. Clinical symptoms suggesting mitochondrial dysfunction were analyzed in routine follow-up, and LA and alanine plasma levels were obtained at 6 weeks, 3 months, 6 months, and 12 months in all patients. Elevated alanine levels, together with hyperlactatemia, suggest chronic mitochondrial injury. RESULTS: Most (85%) women received highly active antiretroviral therapy (HAART) during pregnancy (mean duration: 31 weeks) and zidovudine during labor (93%). Most (96%) children received zidovudine alone. Hyperlactatemia with hyperalaninemia was detected in 63 children in at least 1 of the measurements. Mean LA levels were significantly higher in children who were exposed to nucleoside analogue reverse transcriptase inhibitors than in control subjects (2.88 vs 1.61 at 6 weeks, 2.78 vs 1.49 at 3 months, 1.89 vs 1.39 at 6 months, and 1.71 vs 1.24 at 12 months; peak levels: 8.06, 10.1, 7.28, and 4.48 mmol/L, respectively). In 44 patients, LA levels progressed spontaneously to normality within the first year of life. Three girls presented a slight and self-limited delay in psychomotor development, with LA peak levels of 7.3, 4.0, and 4.6 mmol/L. Only the gestational use of didanosine was associated with a higher risk of hyperlactatemia. CONCLUSIONS: In our series, almost half of the children (63 of 127) who were exposed to nucleoside analogues developed benign and self-limited hyperlactatemia. When symptomatic, nucleoside analogue-induced toxicity affected neurologic development.

Alanine↗
PubMed2005

Building the mitochondrial proteome.

Mitochondria are essential organelles for cellular homeostasis. A variety of pathologies including cancer, myopathies, diabetes, obesity, aging and neurodegenerative diseases are linked to mitochondrial dysfunction. Therefore, mapping the different components of mitochondria is of particular interest to gain further understanding of such diseases. In recent years, proteomics-based approaches have been developed in attempts to determine the complete set of mitochondrial proteins in yeast, plants and mammals. In addition, proteomics-based methods have been applied not only to the analysis of protein function in the organelle, but also to identify biomarkers for diagnosis and therapeutic targets of specific pathologies associated with mitochondria. Altogether, it is becoming clear that proteomics is a powerful tool not only to identify currently unknown components of the mitochondrion, but also to study the different roles of the organelle in cellular homeostasis.

Animals↗
PubMed1986

New technique for the isolation of functional rat pancreatic mitochondria and its application to models of pancreatic injury.

The role of mitochondria in the initiation or promotion of pancreatic pathologic conditions has not been clearly delineated. In this context, it has recently been suggested that abnormal mitochondrial function may account for the fat accumulation observed in pancreatic acinar cells in alcoholism. To study these issues, we developed a method for the isolation of functional mitochondria from the rat pancreas. The resultant mitochondrial pellet possessed oligomycin-insensitive Mg2+-adenosine triphosphatase (ATPase) activity, and coupled respiration could be demonstrated in the presence of EDTA only after Mg2+ had been excluded from the incubation medium. Albumin was also a requirement for the demonstration of coupled respiration in vitro. When this new technique was applied to a rat model of alcohol-induced pancreatic steatosis, no mitochondrial dysfunction was demonstrated, suggesting that some other mechanism is responsible for fat accumulation in pancreatic acinar cells after long-term ethanol consumption. In contrast, DL-ethionine administration to rats produced partial or total uncoupling of mitochondrial respiration in the absence of morphologic evidence of mitochondrial injury.

Adenosine Diphosphate↗
PubMed1993

Identification of the gene encoding the mitochondrial elongation factor G in mammals.

Protein synthesis in cytosolic and rough endoplasmic reticulum associated ribosomes is directed by factors, many of which have been well characterized. Although these factors have been the subject of intense study, most of the corresponding factors regulating protein synthesis in the mitochondrial ribosomes remain unknown. In this report we present the cloning and initial characterization of the gene encoding the rat mitochondrial elongation factor-G (rEF-Gmt). The rat gene encoding EF-Gmt (rMef-g) maps to rat chromosome 2 and it is expressed in all tissues with highest levels in liver, thymus and brain. Its DNA sequence predicts a 752 amino acid protein exhibiting 72% homology to the yeast Saccharomyces cerevisiae mitochondrial elongation factor-G (YMEF-G), 62% and 61% homology to the Thermus thermophilus and E. coli elongation factor-G (EF-G) respectively and 52% homology to the rat elongation factor-2 (EF-2). The deduced amino acid sequence of EF-G contains characteristic motifs shared by all GTP binding proteins. Therefore, similarly to other elongation factors, the enzymatic function of EF-Gmt is predicted to depend on GTP binding and hydrolysis. EF-Gmt differs from its cytoplasmic homolog, EF-2, in that it contains an aspartic acid residue at amino acid position 621 which corresponds to the EF-2 histidine residue at position 715. Since this histidine residue, following posttranslational modification into diphthamide, appears to be the sole cellular target of diphtheria toxin and Pseudomonas aeruginosa endotoxin A, we conclude that EF-Gmt will not be inactivated by these toxins. The severe effects of these toxins on protein elongation in tissues expressing EF-Gmt suggest that EF-Gmt and EF-2 exhibit nonoverlapping functions. The cloning and characterization of the mammalian mitochondrial elongation factor G will permit us to address its role in the regulation of normal mitochondrial function and in disease states attributed to mitochondrial dysfunction.

Animals↗
PubMed1987

Defects in oxidative phosphorylation. Biochemical investigations in skeletal muscle and expression of the lesion in other cells.

Mitochondria are very vulnerable to genetic and environmental damage. If a patient is suspected of having a mitochondrial disease, elevated blood lactate, lowered blood free carnitine, abnormal urinary organic acids and carnitine esters and tissue histopathology may help with the diagnosis. For biochemical assessment of the defect, muscle is the tissue of choice even when involvement of other organs like heart or brain is more prominent. We have studied isolated muscle mitochondria and homogenates from muscle biopsies in 250 patients, and have detected in more than one third mitochondrial defects in oxidative phosphorylation, dehydrogenases, non-redox enzymes catalyzing synthesis of fuel molecules and in the carnitine system. Several patients showed more than one defect. We have selected eight patients to illustrate how a relatively simple series of investigations in both isolated mitochondria and homogenate can be used for the identification of defects in oxidative phosphorylation in a small amount of muscle (200 mg or more). Identification of the defect(s) is important since it may provide the basis for rational treatment. A minority of the patients recovered partly or completely, which is unique in treatment of inborn errors of subcellular organelles. An important aspect of mitochondrial dysfunction is the tissue specificity. The defect may be systemic but is often clinically expressed in only one or a few tissues. Rarely, tissue-specific defects can be understood on the basis of tissue-specificity of mitochondrial (iso-)enzymes. Mitochondrial deficiencies of all biotin enzymes and most CoA-linked enzymes are expressed in fibroblasts; most respiratory chain defects are not. When mitochondrial ATP synthesis has been compromised by a mitochondrial defect, secondary lesions may be generated by changes in mitochondrial protein synthesis, activated proteases and phospholipases, increased matrix CoA and resulting carnitine deficiency, decrease in Krebs cycle intermediates and increased free radical formation and lipid peroxidation.

Adolescent↗
PubMed1984

Aminoglycoside-induced functional and biochemical defects in the renal cortex.

The first site of aminoglycoside-cell interaction occurs at the plasma membrane of renal proximal tubular cells which have been shown to selectively transport and accumulate these drugs. Depression of apical membrane transport of organic base, low-molecular-weight protein, and glucose, together with loss of brush border membrane enzymes and phospholipids in the urine which results in altered phospholipid composition of this membrane, occurs early in the course of aminoglycoside administration. Less well appreciated are the alterations which occur at the basolateral membrane. These include decreased transport of organic bases, Ca2+, Na2+, and K+; increased organic acid transport; decreased activity of Na+-K+ ATPase and adenylate cyclase; decreased calcium content; and altered phospholipid composition. Many of these changes are evident within 90 min of a single injection of drug. Lysosomal dysfunction is manifested by the accumulation of phospholipids in the form of myeloid bodies consequent to the inhibition of lysosomal phospholipases by aminoglycosides. Labilization of lysosomes in vivo has been postulated to be a mechanism of cell injury. Mitochondrial dysfunction attributed to aminoglycosides includes impaired respiration, inhibition of Mg2+ binding, inhibition of Ca2+ uptake, increased permeability to monovalent cations, decreased ammoniagenesis, and decreased gluconeogenesis. However, it remains unclear how the drug gains access to mitochondria in vivo in order to initiate the functional derangements. It is evident that aminoglycosides cause multiple metabolic derangements at multiple sites within renal proximal tubular cells. At present the available evidence does not identify which, if any, of these drug effects is responsible for initiating the injury cascade. The strong possibility exists that aminoglycoside nephrotoxicity reflects the net impact of multiple minor metabolic derangements which individually are of little significance but when added together seriously compromise the cell's ability to maintain its structural and functional integrity.

Aminoglycosides↗
PubMed2000

Astroglial trophic support and neuronal cell death: influence of cellular energy level on type of cell death induced by mitochondrial toxin in cultured rat cortical neurons.

Previous in vivo and in vitro analyses have shown that both necrosis and apoptosis are involved in neuronal cell death induced by energy impairment caused by mitochondrial dysfunction. However, little is known about the key factors that determine whether the cells undergo necrosis or apoptosis. In the present study, we analyzed neuronal cell death induced by 3-nitropropionic acid (3-NP), an irreversible inhibitor of mitochondrial complex II, in a primary culture system of rat cortical neurons. The neurons were maintained for a week in coculture with astroglial cells, and then they were treated with 3-NP in the presence or absence of astroglial cells. As judged from morphological (Hoechst 33258 staining) and biochemical (DNA fragmentation and caspase activation) analyses, the cortical neurons appeared to die through an apoptotic process after 3-NP treatment in the presence of astroglial cells. However, caspase inhibitors did not suppress the 3-NP-induced cell death, suggesting the involvement of a caspase-independent pathway of 3-NP-induced neuronal cell death in the presence of astroglial cells. On the other hand, 3-NP induced necrotic cell death within 1 day in the absence of astroglial cells, following a rapid decrease in intracellular ATP level. These changes were attenuated by the presence of astroglial cells or the addition of astroglial conditioned medium. These results suggest that astroglial trophic support influences the alteration of the intracellular energy state in 3-NP-treated neurons and consequently determines the type of neuronal cell death, apoptosis or necrosis.

Adenosine Triphosphate↗
PubMed2005

Impaired energy metabolism after co-exposure to lead and ethanol.

The neurotoxic effects of lead are controlled by a number of nutritional, physiological and environmental factors. One such factor, ethanol, might affect the neurotoxicity of lead by regulating its absorption and distribution. However, there is little information regarding the possible biochemical mechanism by which ethanol might be affecting the state of neuronal functions in lead-exposed individuals. Therefore, the present investigation involved the effect of alcohol (3 g/kg body weight, intragastrically, for 8 weeks) on lead-induced (50 mg/kg body weight, intragastrically, for 8 weeks) mitochondrial dysfunction in adult rat brain. Ethanol was found to enhance the toxic effects of lead in terms of decreased cellular energy reserves (ATP levels). Co-exposure to lead and ethanol caused marked decline in the rate of mitochondrial respiration as compared to lead alone. Further the activities of various components of the electron transport chain, viz. NADH dehydrogenase, succinate dehydrogenase and cytochrome oxidase depicted a significant decrease in the lead and ethanol co-exposed rats as compared to the lead-treated group. The results of the present study reflect that ethanol makes adult rat brain more vulnerable to the neurotoxic effects of lead in terms of altered mitochondrial energy metabolism.

Adenosine Triphosphate↗
PubMed2006

Mitochondrial involvement in nitric oxide-induced cellular death in cortical neurons in culture.

Nitric oxide (NO) is an unstable molecule with physiological and pathological properties. In brain, NO acts as a modulator of neurotransmission as well as a protector against neuronal death from several death stimuli. However, beside this protector effect, high NO concentrations produce neuronal death by a mechanism in which the caspase pathway is implicated. In this work, we demonstrate that in cortical neurons the NO toxicity is mediated by mitochondrial dysfunction. SNAP, an NO donor, induces apoptosis in these cells because it 1) increases the p53 and 2) induces cytochrome c release and activation of caspase-9 and caspase-3. SNAP also induces necrosis, through 1) breakdown of the mitochondrial membrane potential, 2) ATP decrease, 3) ROS formation, and 4) LDH and ATP release, indicative of oxidative stress and death by necrosis. To sum up, in cortical neurons, high NO concentrations produced cellular death by both an apoptotic and a necrotic mechanism in which the mitochondria are implicated.

Adenosine Triphosphate↗
PubMed1996

Accumulation of somatic nucleotide substitutions in mitochondrial DNA associated with the 3243 A-to-G tRNA(leu)(UUR) mutation in encephalomyopathy and cardiomyopathy.

To understand the pathogenesis of mitochondrial encephalomyopathy and cardiomyopathy, we analyzed the sequence heterogeneity of the skeletal muscle mitochondrial DNA from a patient with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS). A mtDNA segment of 347 bp amplified from the total DNA was cloned into a vector. Analysis of 60 independent clones (20,800 bp in total) revealed the 3243 A-->G transition in all the sequenced clones and additional nucleotide substitutions at 5 sites in 10 clones. The frequency of mutant clones (10/60) in the MELAS patient was significantly higher [chi2 = 10.909, P < 0.05] than that in an age-matched skeletal muscle control (0/60) as well as in a normal placenta (2/60). These results support our hypothesis that secondary somatic mtDNA mutations can be initiated by the 3243 A-->G mutation and that the accumulation of somatic mutation in individuals with deleterious inherited mitochondrial genotype can contribute to the progressive mitochondrial dysfunction in MELAS.

Adult↗
PubMed2004

Mitochondrial disease in flies.

The Drosophila mutant technical knockout (tko), affecting the mitochondrial protein synthetic apparatus, exhibits respiratory chain deficiency and a phenotype resembling various features of mitochondrial disease in humans (paralytic seizures, deafness, developmental retardation). We are using this mutant to analyse the cellular and genomic targets of mitochondrial dysfunction, and to identify ways in which the phenotype can be alleviated. Transgenic expression of wild-type tko in different patterns in the mutant background reveals critical times and cell-types for production of components of the mitochondrial disease-like phenotype. Mitochondrial bioenergy deficit during the period of maximal growth, as well as in specific parts of the nervous system, appears to be most deleterious. Inbreeding of tko mutant lines results in a systematic improvement in all phenotypic parameters tested. The resulting sub-lines can be used for genetic mapping and transcriptomic analysis, revealing clues as to the genes and pathways that can modify mitochondrial disease-like phenotypes in a model metazoan.

Animals↗
PubMed2005

Mitochondrial energy metabolism is markedly impaired by D-2-hydroxyglutaric acid in rat tissues.

Tissue accumulation of high amounts of D-2-hydroxyglutaric acid (DGA) and l-2-hydroxyglutaric acid (LGA) is the biochemical hallmark of the inherited neurometabolic disorders D-2-hydroxyglutaric aciduria (DHGA) and l-2-hydroxyglutaric aciduria (LHGA), respectively. Patients affected by DHGA predominantly present neurological and cardiomuscular symptoms, while those with LHGA have mainly severe neurological symptoms. Lactic aciduria and/or lactic acidemia may also occur in both disorders, suggesting mitochondrial dysfunction. We have previously reported that cytochrome c oxidase (COX) activity is severely inhibited by DGA in rat cerebral cortex and human skeletal muscle. In the present study, we initially evaluated the role of DGA and LGA on the mitochondrial respiratory chain complex activities, as well as CO2 on production in cardiac and skeletal muscle from 30-day-old Wistar rats. DGA significantly inhibited COX and ATP synthase (F0F1-ATP synthase) activities, in contrast to the other activities of the respiratory chain enzymes which were not affected by DGA in both muscular tissues. In addition, CO2 production was also markedly reduced by DGA in rat skeletal and cardiac muscles. On the other hand, LGA did not interfere with any of the respiratory chain complex activities studied, neither with CO2 generation. We also measured mitochondrial respiratory parameters in rat brain mitochondrial preparations in the presence of DGA and LGA. Both metabolites significantly lowered the respiratory control ratio in the presence of glutamate/malate and succinate. Since the metabolites stimulated oxygen consumption in state IV and compromised ATP formation, it can be presumed that these organic acids might act as endogenous uncouplers of mitochondria respiration. Moreover, COX activity linked to TMPD-ascorbate was significantly reduced by DGA in the brain mitochondrial enriched fractions. Finally, DGA and LGA reduced cell viability of rat cerebral cortex slices, as determined by the MTT assay. In case our in vitro data also occur in vivo, it may be presumed that impairment of energy metabolism may contribute to the understanding of the clinical features mainly of patients affected by DHGA.

Animals↗
PubMed2007

Mitochondrial rRNA and tRNA and hearing function.

The human ear is a delicate sensory apparatus of hearing for normal communication, and its proper functioning is highly dependent on mitochondrial oxidative phosphorylation. The first mitochondrial point mutation for nonsyndromic and aminoglycoside-induced hearing loss was identified in 1993. Since then a number of inherited mitochondrial mutations have been implicated in hearing loss. Most of the molecular defects responsible for mitochondrial disorder-associated hearing loss are mutations in the 12S rRNA gene and tRNA genes. In this review, after a short description of normal hearing mechanisms and mitochondrial genetics, we outline the recent advances that have been made in the identification of deafness-associated mitochondrial mutations, and discuss how mitochondrial dysfunction contributes to hearing loss.

Aminoglycosides↗
PubMed2005

Rapid directional shift of mitochondrial DNA heteroplasmy in animal tissues by a mitochondrially targeted restriction endonuclease.

Frequently, mtDNA with pathogenic mutations coexist with wild-type genomes (mtDNA heteroplasmy). Mitochondrial dysfunction and disease ensue only when the proportion of mutated mtDNAs is high, thus a reduction in this proportion should provide an effective therapy for these disorders. We developed a system to decrease specific mtDNA haplotypes by expressing a mitochondrially targeted restriction endonuclease, ApaLI, in cells of heteroplasmic mice. These mice have two mtDNA haplotypes, of which only one contains an ApaLI site. After transfection of cultured hepatocytes with mitochondrially targeted ApaLI, we found a rapid, directional, and complete shift in mtDNA heteroplasmy (2-6 h). We tested the efficacy of this approach in vivo, by using recombinant viral vectors expressing the mitochondrially targeted ApaLI. We observed a significant shift in mtDNA heteroplasmy in muscle and brain transduced with recombinant viruses. This strategy could prevent disease onset or reverse clinical symptoms in patients harboring certain heteroplasmic pathogenic mutations in mtDNA.

Adenoviridae↗
PubMed2005

Mitochondriotropic liposomes.

Mitochondrial dysfunction contributes to a large variety of human disorders, ranging from neurodegenerative and neuromuscular diseases, obesity, and diabetes to ischemia-reperfusion injury and cancer. Increasing pharmacological efforts toward therapeutic interventions have been made leading to the emergence of "Mitochondrial Medicine" as a new field of biomedical research. The identification of molecular mitochondrial drug targets in combination with the development of methods for selectively delivering biologically active molecules to the site of mitochondria will eventually launch a multitude of new therapies for the treatment of mitochondria-related diseases, which are based either on the selective protection, repair, or eradication of cells. Yet, while tremendous efforts are being undertaken to identify new mitochondrial drugs and drug targets, the development of mitochondria-specific drug carrier systems is lagging behind. To ensure a high efficiency of current and future mitochondrial therapeutics, delivery systems need to be developed, which are able to selectively transport biologically active molecules to and into mitochondria within living human cells. In this study we present the first data demonstrating that conventional liposomes can be rendered mitochondria-specific via the attachment of known mitochondriotropic residues to the liposomal surface.

Bromides↗