scholarly journals Mitochondrial bioactivation of cysteine S-conjugates and 4-thiaalkanoates: Implications for mitochondrial dysfunction and mitochondrial diseases

1995 ◽  
Vol 1271 (1) ◽  
pp. 51-57 ◽  
Author(s):  
M.W. Anders
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Diseases

scholarly journals Epilepsy in Mitochondrial Diseases—Current State of Knowledge on Aetiology and Treatment

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 532
Author(s):  
Dorota Wesół-Kucharska ◽  
Dariusz Rokicki ◽  
Aleksandra Jezela-Stanek
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Clinical Picture ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Mitochondrial Diseases ◽  
Energy Deficit ◽  
Atp Production ◽  
Current State

Mitochondrial diseases are a heterogeneous group of diseases resulting from energy deficit and reduced adenosine triphosphate (ATP) production due to impaired oxidative phosphorylation. The manifestation of mitochondrial disease is usually multi-organ. Epilepsy is one of the most common manifestations of diseases resulting from mitochondrial dysfunction, especially in children. The onset of epilepsy is associated with poor prognosis, while its treatment is very challenging, which further adversely affects the course of these disorders. Fortunately, our knowledge of mitochondrial diseases is still growing, which gives hope for patients to improve their condition in the future. The paper presents the pathophysiology, clinical picture and treatment options for epilepsy in patients with mitochondrial disease.

scholarly journals GDF-15 Is Elevated in Children with Mitochondrial Diseases and Is Induced by Mitochondrial Dysfunction

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0148709 ◽  
Author(s):  
Raquel Montero ◽  
Delia Yubero ◽  
Joan Villarroya ◽  
Desiree Henares ◽  
Cristina Jou ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Diseases

scholarly journals Gene Therapeutic Approaches for the Treatment of Mitochondrial Dysfunction in Parkinson’s Disease

2021 ◽  
Author(s):  
Jannik Prasuhn ◽  
Norbert Brüggemann
Keyword(s):  
Mitochondrial Dysfunction ◽  
Disease Onset ◽  
Treatment Strategies ◽  
Mitochondrial Diseases ◽  
Therapeutic Approaches ◽  
Treatment Target ◽  
Gene Therapies ◽  
Parkinsonian Disorders ◽  
Potential Strategy ◽  
Viable Treatment

Background. Mitochondrial dysfunction has been identified as a pathophysiological hallmark of disease onset and progression in patients with Parkinsonian disorders. Besides the overall emergence of gene therapies in treating these patients, this highly relevant molecular concept has not yet been defined as a target for gene therapeutic approaches. Methods. This narrative review will discuss the experimental evidence suggesting mitochondrial dysfunction as a viable treatment target in patients with monogenic and idiopathic Parkinson’s disease. In addition, we will focus on general treatment strategies and crucial challenges which need to be overcome. Results. Our current understanding of mitochondrial biology in parkinsonian disorders opens up the avenue for viable treatment strategies in Parkinsonian disorders. Insights can be obtained from primary mitochondrial diseases. However, substantial knowledge gaps and unique challenges of mitochondria-targeted gene therapies need to be addressed to provide innovative treatments in the future. Conclusions. Mitochondria-targeted gene therapies are a potential strategy to improve an important primary disease mechanism in Parkinsonian disorders. However, further studies are needed to address the unique design challenges for mitochondria-targeted gene therapies.

scholarly journals Mitochondrial Dysfunction and Multiple Sclerosis

Biology ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 37 ◽  
Author(s):  
Isabella Peixoto de Barcelos ◽  
Regina M. Troxell ◽  
Jennifer S. Graves
Keyword(s):  
Multiple Sclerosis ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Diseases ◽  
Mitochondrial Respiratory Chain ◽  
Channel Changes ◽  
Respiratory Chain Deficiency ◽  
Inflammatory Phase ◽  
Chronic Oxidative Stress ◽  
Progressive Neurodegeneration ◽  
The Central Nervous System

In recent years, several studies have examined the potential associations between mitochondrial dysfunction and neurodegenerative diseases such as multiple sclerosis (MS), Parkinson’s disease and Alzheimer’s disease. In MS, neurological disability results from inflammation, demyelination, and ultimately, axonal damage within the central nervous system. The sustained inflammatory phase of the disease leads to ion channel changes and chronic oxidative stress. Several independent investigations have demonstrated mitochondrial respiratory chain deficiency in MS, as well as abnormalities in mitochondrial transport. These processes create an energy imbalance and contribute to a parallel process of progressive neurodegeneration and irreversible disability. The potential roles of mitochondria in neurodegeneration are reviewed. An overview of mitochondrial diseases that may overlap with MS are also discussed, as well as possible therapeutic targets for the treatment of MS and other neurodegenerative conditions.

scholarly journals Mitochondrial retrograde signalling in neurological disease

2020 ◽  
Vol 375 (1801) ◽  
pp. 20190415 ◽  
Author(s):  
Lucy Granat ◽  
Rachel J. Hunt ◽  
Joseph M. Bateman
Keyword(s):  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Neurodevelopmental Disorders ◽  
Neurological Disease ◽  
Neurological Diseases ◽  
Nuclear Gene ◽  
Mitochondrial Diseases ◽  
Autism Spectrum ◽  
Signalling Pathways ◽  
Retrograde Signalling

Neuronal mitochondrial dysfunction causes primary mitochondrial diseases and likely contributes to neurodegenerative diseases including Parkinson's and Alzheimer's disease. Mitochondrial dysfunction has also been documented in neurodevelopmental disorders such as tuberous sclerosis complex and autism spectrum disorder. Only symptomatic treatments exist for neurodevelopmental disorders, while neurodegenerative diseases are largely untreatable. Altered mitochondrial function activates mitochondrial retrograde signalling pathways, which enable signalling to the nucleus to reprogramme nuclear gene expression. In this review, we discuss the role of mitochondrial retrograde signalling in neurological diseases. We summarize how mitochondrial dysfunction contributes to neurodegenerative disease and neurodevelopmental disorders. Mitochondrial signalling mechanisms that have relevance to neurological disease are discussed. We then describe studies documenting retrograde signalling pathways in neurons and glia, and in animal models of neuronal mitochondrial dysfunction and neurological disease. Finally, we suggest how specific retrograde signalling pathways can be targeted to develop novel treatments for neurological diseases. This article is part of the theme issue ‘Retrograde signalling from endosymbiotic organelles’.

scholarly journals Generation of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hideki Maeda ◽  
Daisuke Kami ◽  
Ryotaro Maeda ◽  
Akira Shikuma ◽  
Satoshi Gojo
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Respiratory Function ◽  
Disease Patient ◽  
Mitochondrial Diseases ◽  
Wild Type ◽  
Mutant Genotype ◽  
Isolated Mitochondria ◽  
Wide Range

AbstractMitochondrial diseases currently have no cure regardless of whether the cause is a nuclear or mitochondrial genome mutation. Mitochondrial dysfunction notably affects a wide range of disorders in aged individuals, including neurodegenerative diseases, cancers, and even senescence. Here, we present a procedure to generate mitochondrial DNA-replaced somatic cells with a combination of a temporal reduction in endogenous mitochondrial DNA and coincubation with exogeneous isolated mitochondria. Heteroplasmy in mitochondrial disease patient-derived fibroblasts in which the mutant genotype was dominant over the wild-type genotype was reversed. Mitochondrial disease patient-derived fibroblasts regained respiratory function and showed lifespan extension. Mitochondrial membranous components were utilized as a vehicle to deliver the genetic materials into endogenous mitochondria-like horizontal genetic transfer in prokaryotes. Mitochondrial DNA-replaced cells could be a resource for transplantation to treat maternal inherited mitochondrial diseases.

scholarly journals Generation of Somatic Mitochondrial DNA-Replaced Cells for Mitochondrial Dysfunction Treatment

2020 ◽  
Author(s):  
Hideki Maeda ◽  
Daisuke Kami ◽  
Ryotaro Maeda ◽  
Akira Shikuma ◽  
Satoshi Gojo
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Pluripotent Stem Cells ◽  
Disease Patient ◽  
Mitochondrial Diseases ◽  
Wild Type ◽  
Mutant Genotype ◽  
Wide Range

AbstractMitochondrial diseases currently have no cure regardless of whether the cause is a nuclear or mitochondrial genome mutation. Mitochondrial dysfunction notably affects a wide range of disorders in aged individuals, including neurodegenerative diseases, cancers, and even senescence. Here, we present a procedure to generate mitochondrial DNA-replaced somatic cells with a combination of a temporal reduction in endogenous mitochondrial DNA and coincubation with exogeneous isolated mitochondria. Heteroplasmy in mitochondrial disease patient-derived fibroblasts in which the mutant genotype was dominant over the wild-type genotype was reversed over the long term, even inducing the production of pluripotent stem cells from the mitochondrial DNA-replaced cells to maintain the genotype without a reversion to the original. Both mitochondrial disease patient-derived and aged fibroblasts could regain respiratory function and showed lifespan extension. Mitochondrial membranous components were utilized as a vehicle to deliver the genetic materials into endogenous mitochondria-like horizontal genetic transfer in prokaryotes. The mitochondrial DNA-replaced cells could be a resource for transplantation to treat not only mitochondrial diseases, but also senescence-related diseases.

Multifunctional radical quenchers as potential therapeutic agents for the treatment of mitochondrial dysfunction

2019 ◽  
Vol 11 (13) ◽  
pp. 1605-1624
Author(s):  
Xun Ji ◽  
Omar M Khdour ◽  
Sidney M Hecht
Keyword(s):  
Mitochondrial Dysfunction ◽  
Small Molecules ◽  
Oxygen Radicals ◽  
Reactive Oxygen ◽  
Mitochondrial Diseases ◽  
Therapeutic Agents ◽  
Oxygen Species ◽  
Design Strategies ◽  
Cellular Models ◽  
Wide Range

Mitochondrial dysfunction is associated with a wide range of human diseases, including neurodegenerative diseases, and is believed to cause or contribute to the etiology of these diseases. These disorders are frequently associated with increased levels of reactive oxygen species. One of the design strategies for therapeutic intervention involves the development of novel small molecules containing redox cores, which can scavenge reactive oxygen radicals and selectively block oxidative damage to the mitochondria. Presently, we describe recent research dealing with multifunctional radical quenchers as antioxidants able to scavenge reactive oxygen radicals. The review encompasses ubiquinone and tocopherol analogs, as well as novel pyri(mi)dinol derivatives, and their ability to function as protective agents in cellular models of mitochondrial diseases.

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