Advances in Mitochondrial Medicine

Enns, Gregory M.

doi:10.1177/2326409817752961

Cited by 2 publications

(3 citation statements)

References 13 publications

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“…RPE cells have a key role in regulating the visual cycle and supporting the survival and maintenance of the functionality of photoreceptor cells (PRCs). Functionally impaired mitochondria and cellular oxidation levels are linked to age-related neurodegenerative diseases, such as AMD [11][12][13][14]. RPE cells are known to be quiescent and their mitochondria are particularly prone to oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

“…In general, autophagy involves a bulky nonselective degradation pathway and selective form which maintains intracellular homeostasis by mediating and degrading cytoplasmic materials, such as misfolded proteins, damaged organelles, lipids and carbohydrates, by target-specific Functionally impaired mitochondria and cellular oxidation levels are linked to age-related neurodegenerative diseases, such as AMD [11][12][13][14]. RPE cells are known to be quiescent and their mitochondria are particularly prone to oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

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Mitophagy in the Retinal Pigment Epithelium of Dry Age-Related Macular Degeneration Investigated in the NFE2L2/PGC-1α-/- Mouse Model

Gurubaran

Viiri

Koskela

et al. 2020

IJMS

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Increased oxidative stress and mitochondrial damage are observed in protein aggregation diseases, such as age-related macular degeneration (AMD). We have recently reported elevated levels of oxidative stress markers, damaged mitochondria, accumulating lysosomal lipofuscin and extracellular drusen-like structures in the retinal pigment epithelial cells (RPE) of the dry AMD-resembling NFE2L2/PGC1α double knockout (dKO) mouse model. Here, we provide evidence of a disturbance in the autolysosomal machinery handling mitochondrial clearance in the RPE cells of one-year-old NFE2L2/PGC1α-deficient mice. Confocal immunohistochemical analysis revealed an upregulation of autophagosome marker microtubule-associated proteins 1A/1B light chain 3B (LC3B) as well as numerous mitophagy markers, such as PTE-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (PARKIN) together with damaged mitochondria. However, we detected no evidence of increased autolysosome formation in transmission electron micrographs or of colocalization of lysosomal marker LAMP2 (lysosome-associated membrane protein 2) and the mitochondrial marker ATP synthase β in confocal micrographs. Interestingly, we observed an upregulation of late autolysosomal fusion Ras-related protein (Rab7) in the perinuclear space of RPE cells together with autofluorescence aggregates. Our results reveal that there is at least a relative decrease of mitophagy in the RPE cells of NFE2L2/PGC1α dKO mice. This further supports the hypothesis that mitophagy is a putative therapy target in AMD-like pathology.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitophagy in the Retinal Pigment Epithelium of Dry Age-Related Macular Degeneration Investigated in the NFE2L2/PGC-1α-/- Mouse Model

Gurubaran

Viiri

Koskela

et al. 2020

IJMS

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“…The knowledge about mitochondria is being constantly supplementated and expanded [30,42,49,51]. The diseases, based on hereditarily determined (primary) or acquired (secondary) mitochondrial dysfunction which was the disruption of energy production as ATP in the process of oxidative phosphorylation, have been detected [17,26,36,38]. MD are displayed by disorders of high energy-dependent nervous, cardiovascular and muscle systems.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial dysfunctions and antihypoxants

Новиков

Левченкова

Ivantsova

et al. 2020

Rev Clin Pharm Drug Ther

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Mitochondrial dysfunctions (an impaired energy metabolism in the mitochondria) are essential in a pathogenesis of many diseases. Aim. The analysis of various mitochondrial dysfunction (MD) type study, as well as evaluation of drugs with an antihypoxic effect in their treatment. Methods. Collection, systematization and analysis of experimental and clinical data of current scientific research about the problem. Results. The mitochondrial dysfunctions can be caused by genetic disorders of the mitochondrial or nuclear genome (the primary MD or the mitochondrial diseases), as well as structural, functional and biochemical defects of mitochondria caused by other diseases (the secondary MD). MD are characterized by impaired tissue respiration, ATP synthesis deficiency and decreased energy metabolism. The clinical implications of MD are polysystemic and polymorphic. One of the biochemical sign of MD is the lactic acidosis. There are certain difficulties with the early diagnosis of primary MD. It is suggested to use complete exome sequencing among patients with a clinical suspicion on mitochondrial disease. The energotropic pharmacotherapy including drugs with an antihypoxic effect is used for MD treatment. It is more rational to use the drug combination that influences different stages of energy production. The combinations of L-carnitine, coenzyme Q10, cytochrome C and succinate-containing drugs are frequently used for MD. However, the usage of energotropic and antihypoxic drugs is not able to cure the patients and stop the progression of all disease displays. Conclusion. MD are a multidisciplinary problem, therefore, doctors of any speciality must be competent in the MD diagnosis and treatment. The use of energotropic agents in the MD treatment requires further research. Numerous issues remain open (daily drug doses choice, treatment duration, rational combinations). The phenotype variability and the uniqueness of diagnosed cases, clinical and genetic differences between patient groups with mitochondrial diseases fail to create homogeneous samplings for therapy effectiveness and safety analysis. The literature data are the results of different degrees of reliability. The international efforts are needed to unify studies of related mitochondrial disorders, which, in combination with a constant improvement of MD pathogenesis knowledge will allow to develop more effective treatment regimens.

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Advances in Mitochondrial Medicine

Cited by 2 publications

References 13 publications

Mitophagy in the Retinal Pigment Epithelium of Dry Age-Related Macular Degeneration Investigated in the NFE2L2/PGC-1α-/- Mouse Model

Mitophagy in the Retinal Pigment Epithelium of Dry Age-Related Macular Degeneration Investigated in the NFE2L2/PGC-1α-/- Mouse Model

Mitochondrial dysfunctions and antihypoxants

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