Mitochondrial DNA copy number in human disease: the more the better?

FEBS Letters, Год журнала: 2020, Номер 595(8), С. 976 - 1002

Опубликована: Дек. 12, 2020

Most of the genetic information has been lost or transferred to nucleus during evolution mitochondria. Nevertheless, mitochondria have retained their own genome that is essential for oxidative phosphorylation (OXPHOS). In mammals, a gene‐dense circular mitochondrial DNA (mtDNA) about 16.5 kb encodes 13 proteins, which constitute only 1% proteome. Mammalian mtDNA present in thousands copies per cell and mutations often affect fraction them. pathogenic human are recessive cause OXPHOS defects if above certain critical threshold. However, emerging evidence strongly suggests proportion mutated not determinant disease but also absolute copy number matters. this review, we critically discuss current knowledge role regulation various types diseases, including disorders, neurodegenerative disorders cancer, ageing. We provide an overview new exciting therapeutic strategies directly manipulate restore diseases.

Язык: Английский

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Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention

Signal Transduction and Targeted Therapy, Год журнала: 2021, Номер 6(1)

Опубликована: Июнь 28, 2021

Remarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that decline of physical function often initiates by cell senescence organ ageing. Epigenetic dynamics immunometabolic reprogramming link to alterations cellular response intrinsic extrinsic stimuli, representing current hotspots as they not only (re-)shape individual identity, but also involve fate decision. This review focuses on present findings emerging concepts epigenetic, inflammatory, metabolic regulations consequences process. Potential therapeutic interventions targeting regulatory mechanisms, using state-of-the-art techniques are discussed.

Язык: Английский

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Extreme heterogeneity of human mitochondrial DNA from organelles to populations

Nature Reviews Genetics, Год журнала: 2020, Номер 22(2), С. 106 - 118

Опубликована: Сен. 28, 2020

Язык: Английский

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Evolving concepts in NAD+ metabolism

Cell Metabolism, Год журнала: 2021, Номер 33(6), С. 1076 - 1087

Опубликована: Апрель 29, 2021

Язык: Английский

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Mitochondrial disease in adults: recent advances and future promise

The Lancet Neurology, Год журнала: 2021, Номер 20(7), С. 573 - 584

Опубликована: Июнь 16, 2021

Язык: Английский

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NAD ⁺ homeostasis in human health and disease

EMBO Molecular Medicine, Год журнала: 2021, Номер 13(7)

Опубликована: Май 27, 2021

Язык: Английский

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Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction

Redox Biology, Год журнала: 2021, Номер 43, С. 101988 - 101988

Опубликована: Апрель 24, 2021

Nicotinamide adenine dinucleotide (NAD) is a REDOX cofactor and metabolite essential for neuronal survival. Glaucoma common neurodegenerative disease in which levels of NAD decline. We assess the effects nicotinamide (a precursor to NAD) on retinal ganglion cells (the affected neuron glaucoma) normal physiological conditions across range glaucoma relevant insults including mitochondrial stress axon degenerative insults. demonstrate cell somal, axonal, dendritic neuroprotection by rodent models represent isolated ocular hypertensive, degenerative, performed metabolomics enriched small molecular weight metabolites retina, optic nerve, superior colliculus demonstrates that hypertension induces widespread metabolic disruption, consistent changes α-ketoglutaric acid, creatine/creatinine, homocysteine, glycerophosphocholine. This disruption prevented nicotinamide. provides further neuroprotective increasing oxidative phosphorylation, buffering preventing stress, size motility whilst simultaneously dampening action potential firing frequency. These data support continued determination utility long-term treatment as therapy human glaucoma.

Язык: Английский

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Mitochondria at the crossroads of health and disease

Cell, Год журнала: 2024, Номер 187(11), С. 2601 - 2627

Опубликована: Май 1, 2024

Mitochondria reside at the crossroads of catabolic and anabolic metabolism—the essence life. How their structure function are dynamically tuned in response to tissue-specific needs for energy, growth repair, renewal is being increasingly understood. respond intrinsic extrinsic stresses can alter cell organismal by inducing metabolic signaling within cells distal tissues. Here, we review how centrality mitochondrial functions manifests health a broad spectrum diseases aging.

Язык: Английский

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Association between Dietary Niacin Intake and Migraine among American Adults: National Health and Nutrition Examination Survey

Nutrients, Год журнала: 2022, Номер 14(15), С. 3052 - 3052

Опубликована: Июль 25, 2022

Migraine is related to brain energy deficiency. Niacin a required coenzyme in mitochondrial metabolism. However, the relationship between dietary niacin and migraines remains uncertain. We aimed evaluate migraine. This study used cross-sectional data from people over 20 years old who took part National Health Nutrition Examination Survey 1999 2004, collecting details on their severe headaches or migraines, intake, several other essential variables. There were 10,246 participants, with 20.1% (2064/10,246) experienced migraines. Compared individuals lower consumption Q1 (≤12.3 mg/day), adjusted OR values for intake migraine Q2 (12.4−18.3 Q3 (18.4−26.2 Q4 (≥26.3 mg/day) 0.83 (95% CI: 0.72−0.97, p = 0.019), 0.74 0.63−0.87, < 0.001), 0.72 0.58−0.88, respectively. The association exhibited an L-shaped curve (nonlinear, 0.011). of developing was 0.975 0.956−0.994, 0.011) participants 21.0 mg/day. link US adults L-shaped, inflection point roughly

Язык: Английский

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Healthy aging and muscle function are positively associated with NAD+ abundance in humans

Nature Aging, Год журнала: 2022, Номер 2(3), С. 254 - 263

Опубликована: Фев. 17, 2022

Язык: Английский

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