Mitophagy plays a central role in mitochondrial ageing

Diot, Alan; Morten, Karl; Poulton, Joanna

doi:10.1007/s00335-016-9651-x

Cited by 92 publications

(71 citation statements)

References 209 publications

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“…[44], [45], [46], [47] There are limited data on the role of mitophagy in DKD progression and whether targeting mitophagy regulates renal pathological changes in DKD. Therefore, we investigated the protective effects of mitoQ on tubular cells and whether this effect was achieved by regulating mitophagy under hyperglycemia conditions.…”

Section: Discussionmentioning

confidence: 99%

The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1

et al. 2017

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Mitochondria play a crucial role in tubular injury in diabetic kidney disease (DKD). MitoQ is a mitochondria-targeted antioxidant that exerts protective effects in diabetic mice, but the mechanism underlying these effects is not clear. We demonstrated that mitochondrial abnormalities, such as defective mitophagy, mitochondrial reactive oxygen species (ROS) overexpression and mitochondrial fragmentation, occurred in the tubular cells of db/db mice, accompanied by reduced PINK and Parkin expression and increased apoptosis. These changes were partially reversed following an intraperitoneal injection of mitoQ. High glucose (HG) also induces deficient mitophagy, mitochondrial dysfunction and apoptosis in HK-2 cells, changes that were reversed by mitoQ. Moreover, mitoQ restored the expression, activity and translocation of HG-induced NF-E2-related factor 2 (Nrf2) and inhibited the expression of Kelch-like ECH-associated protein (Keap1), as well as the interaction between Nrf2 and Keap1. The reduced PINK and Parkin expression noted in HK-2 cells subjected to HG exposure was partially restored by mitoQ. This effect was abolished by Nrf2 siRNA and augmented by Keap1 siRNA. Transfection with Nrf2 siRNA or PINK siRNA in HK-2 cells exposed to HG conditions partially blocked the effects of mitoQ on mitophagy and tubular damage. These results suggest that mitoQ exerts beneficial effects on tubular injury in DKD via mitophagy and that mitochondrial quality control is mediated by Nrf2/PINK.

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Section: Discussionmentioning

confidence: 99%

The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1

et al. 2017

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“…Mitophagy is an indispensable quality control mechanism constantly removing damaged and dysfunctional mitochondria to maintain optimal function of different tissues in the body. Impaired mitophagy in different tissues has been associated with frailty, cardiovascular, neurodegenerative, and metabolic diseases in obesity and ageing . Recently, studies showed that impaired mitophagy is linked to macrophage lineage, which is crucial to age‐related changes and chronic inflammation in obesity .…”

Section: Obesity Reinforces Machinery Of Ageingmentioning

confidence: 99%

“…Impaired mitophagy in different tissues has been associated with frailty, cardiovascular, neurodegenerative, and metabolic diseases in obesity and ageing. 63,64 Recently, studies showed that impaired mitophagy is linked to macrophage lineage, which is crucial to age-related changes and chronic inflammation in obesity. 65 Accumulation of damaged mitochondria in macrophages due to insufficient mitophagy activates excessive secretion of IL-1β, which enhances macrophage death and compromises macrophage-mediated immunity, tissue repair, and healing.…”

Section: Insufficient Autophagy and Apoptosismentioning

confidence: 99%

Obesity and ageing: Two sides of the same coin

2020

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Summary Conditions and comorbidities of obesity mirror those of ageing and age‐related diseases. Obesity and ageing share a similar spectrum of phenotypes such as compromised genomic integrity, impaired mitochondrial function, accumulation of intracellular macromolecules, weakened immunity, shifts in tissue and body composition, and enhanced systemic inflammation. Moreover, it has been shown that obesity reduces life expectancy by 5.8 years in men and 7.1 years in women after the age of 40. Shorter life expectancy could be because obesity holistically accelerates ageing at multiple levels. Besides jeopardizing nuclear DNA and mitochondrial DNA integrity, obesity modifies the DNA methylation pattern, which is associated with epigenetic ageing in different tissues. Additionally, other signs of ageing are seen in individuals with obesity including telomere shortening, systemic inflammation, and functional declines. This review aims to show how obesity and ageing are “two sides of the same coin” through discussing how obesity predisposes an individual to age‐related conditions, illness, and disease. We will further demonstrate how the mechanisms that perpetuate the early‐onset of chronic diseases in obesity parallel those of ageing.

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“…As an example, 95% of mitochondria in the muscle tissue of a healthy 90‐year‐old man were found to be damaged, compared to no detectable damage in the muscle tissue of a 5‐year‐old child . Impairment of mitophagy, the pathway to eliminate mitochondria, also occurs with age; and this can contribute to the accumulation of damaged mitochondria with mitochondrial DNA (mtDNA) mutations . Consistently, increased mitophagy is protective for mitochondrial health, and is associated with decreased cellular aging in mice and humans and increased lifespan in C. elegans and Drosophila …”

Section: Mitochondria Are Important Determinants Of Agingmentioning

confidence: 99%

The Energy Maintenance Theory of Aging: Maintaining Energy Metabolism to Allow Longevity

Chaudhari

Kipreos

2018

BioEssays

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Fused, elongated mitochondria are more efficient in generating ATP than fragmented mitochondria. In diverse C. elegans longevity pathways, increased levels of fused mitochondria are associated with lifespan extension. Blocking mitochondrial fusion in these animals abolishes their extended longevity. The long-lived C. elegans vhl-1 mutant is an exception that does not have increased fused mitochondria, and is not dependent on fusion for longevity. Loss of mammalian VHL upregulates alternate energy generating pathways. This suggests that mitochondrial fusion facilitates longevity in C. elegans by increasing energy metabolism. In diverse animals, ATP levels broadly decreases with age. Substantial evidence supports the theory that increasing or maintaining energy metabolism promotes the survival of older animals. Increased ATP levels in older animals allow energy-intensive repair and homeostatic mechanisms such as proteostasis that act to prevent cellular aging. These observations support the emerging paradigm that maintaining energy metabolism promotes the survival of older animals.

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Mitophagy plays a central role in mitochondrial ageing

Cited by 92 publications

References 209 publications

The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1

The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1

Obesity and ageing: Two sides of the same coin

The Energy Maintenance Theory of Aging: Maintaining Energy Metabolism to Allow Longevity

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