Search results for "mitochondrial disease"

Analysis of BNIP3 and BNIP3L/Nix expression in cybrid cell lines harboring two LHON-associated mutations.

2019

Mitochondria are key players in cell death through the activation of the intrinsic apoptosis pathway. BNIP3 and BNIP3L/Nix are outer mitochondrial membrane bifunctional proteins which because of containing both BH3 and LIR domains play a role in cellular response to stress by regulation of apoptosis and selective autophagy. Leber’s Hereditary Optic Neuropathy (LHON) is the most common mitochondrial disease in adults, characterized by painless loss of vision caused by atrophy of the optic nerve. The disease in over 90% of cases is caused by one of three mutations in the mitochondrial genome: 11778G>A, 3460G>A or 14484T>C. The pathogenic processes leading to optic nerve degeneration …

Oxidative Stress in Neurodegenerative Diseases: From a Mitochondrial Point of View

2019

Age is the main risk factor for a number of human diseases, including neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, which increasing numbers of elderly individuals suffer. These pathological conditions are characterized by progressive loss of neuron cells, compromised motor or cognitive functions, and accumulation of abnormally aggregated proteins. Mitochondrial dysfunction is one of the main features of the aging process, particularly in organs requiring a high-energy source such as the heart, muscles, brain, or liver. Neurons rely almost exclusively on the mitochondria, which produce the energy required for most of the cel…

Mitochondrial Markers in Aging and Primary Open-Angle Glaucoma

2020

This review focuses on recent progress in understanding the role of mitochondrial markers in the context of mitochondrial dysfunction in glaucoma and discussing new therapeutic approaches to modulate mitochondrial function and potentially lead to improved outcomes in glaucoma.

A spontaneous mitonuclear epistasis converging on Rieske Fe-S protein exacerbates complex III deficiency in mice

2020

We previously observed an unexpected fivefold (35 vs. 200 days) difference in the survival of respiratory chain complex III (CIII) deficient Bcs1lp.S78G mice between two congenic backgrounds. Here, we identify a spontaneous homoplasmic mtDNA variant (m.G14904A, mt-Cybp.D254N), affecting the CIII subunit cytochrome b (MT-CYB), in the background with short survival. We utilize maternal inheritance of mtDNA to confirm this as the causative variant and show that it further decreases the low CIII activity in Bcs1lp.S78G tissues to below survival threshold by 35 days of age. Molecular dynamics simulations predict D254N to restrict the flexibility of MT-CYB ef loop, potentially affecting RISP dyna…

Mitochondrial oxidative injury: a key player in nonalcoholic fatty liver disease.

2020

Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide. NAFLD is tightly linked to the metabolic syndrome, insulin resistance, and oxidative stress. Globally, its inflammatory form, nonalcoholic steatohepatitis (NASH), has become the main cause of liver-related morbidity and mortality, mainly due to liver cirrhosis and primary liver cancer. One hallmark of NASH is the presence of changes in mitochondrial morphology and function that are accompanied by a blocked flow of electrons in the respiratory chain, which increases formation of mitochondrial reactive oxygen species in a self-perpetuating vicious cycle. Consequences are oxidation of DNA bases and …

Clinical and Biochemical Features in a Patient With Mitochondrial Fission Factor Gene Alteration

2018

Mitochondrial Fission Factor (MFF) is part of a protein complex that promotes mitochondria and peroxisome fission. Hitherto, only 5 patients have been reported harboring mutations in MFF, all of them with the clinical features of a very early onset Leigh-like encephalopathy. We report on an 11-year-old boy with epileptic encephalopathy. He presented with neurological regression, epileptic myoclonic seizures, severe intellectual disability, microcephaly, tetraparesis, optic atrophy, and ophthalmoplegia. Brain MRI pattern was compatible with Leigh syndrome. NGS-based analysis of a gene panel for mitochondrial disorders revealed a homozygous c.892C>T (p. Arg298*) in the MFF gene. Fluorescen…

Magnetic Resonance Spectroscopy: principles and clinical applications. Experimental Medicine Reviews

2009

Differential expression of PGC-1α and metabolic sensors suggest age-dependent induction of mitochondrial biogenesis in Friedreich ataxia fibroblasts.

2011

11 pages, 6 figures. PMID:21687738[PubMed] PMCID: PMC3110204

Novel LRPPRC compound heterozygous mutation in a child with early-onset Leigh syndrome French-Canadian type: Case report of an Italian patient

2020

Abstract Background Mitochondrial diseases, also known as oxidative phosphorylation (OXPHOS) disorders, with a prevalence rate of 1:5000, are the most frequent inherited metabolic diseases. Leigh Syndrome French Canadian type (LSFC), is caused by mutations in the nuclear gene (2p16) leucine-rich pentatricopeptide repeat-containing (LRPPRC). It is an autosomal recessive neurogenetic OXPHOS disorder, phenotypically distinct from other types of Leigh syndrome, with a carrier frequency up to 1:23 and an incidence of 1:2063 in the Saguenay-Lac-St Jean region of Quebec. Recently, LSFC has also been reported outside the French-Canadian population. Patient presentation We report a male Italian (Sic…

Molecular oncology focus - is carcinogenesis a 'mitochondriopathy'?

2010

Abstract Mitochondria are sub-cellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and in mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, and some reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients. Nevertheless, a careful reanalysis of methodological criteria and methodology applied in those reports has shown that numerous papers can't be used as relevant sources …