In Brief: Mitophagy: mechanisms and role in human disease

Springer, Maya Z.; Macleod, Kay F.

doi:10.1002/path.4774

Cited by 140 publications

(103 citation statements)

References 5 publications

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“…57,[59][60][61][62] The accumulation of ROS caused by dysregulation of mitophagy and pexophagy plays a central role in inflammation and chronic diseases, such as atherosclerosis and cancer. 57,[59][60][61][62] The accumulation of ROS caused by dysregulation of mitophagy and pexophagy plays a central role in inflammation and chronic diseases, such as atherosclerosis and cancer.…”

Section: Figurementioning

confidence: 99%

Multifaceted roles of ATM in autophagy: From nonselective autophagy to selective autophagy

Liang

Liu

et al. 2019

Cell Biochemistry & Function

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The ataxia-telangiectasia mutated (ATM) protein kinase is best known for its critical nuclear roles in the DNA damage response (DDR), cell cycle checkpoints, and the maintenance of gene stability. In this review, we highlight the multifaceted cytoplasmic functions of ATM in autophagy. We focused on the functions of ATM in nonselective autophagy in cancer. An Oncomine database analysis showed a tight association between ATM and autophagy in various cancers. In particular, its mechanisms in nonselective autophagy, those induced by ionizing radiation (IR), are illustrated in detail and involve the MAPK14 pathway, mTOR pathway, and Beclin1/PI3KIII complexes. Recently, an increasing number of studies revealed that autophagy could also be highly selective. We additionally emphasized the novel roles of ATM in selective autophagy, including mitophagy, pexophagy, and lipophagy. The regulation of these processes mainly involves ATM-PEX5, ATM-AMPK-TSC2-mTORC1-ULK1, PPM1D-ATM-MTOR, PINK I/Parkin, and NAD+/ SIRT1. We aimed to provide new perspectives on the importance of ATM in the diverse field of autophagy. The intricate regulation of ATM in autophagy still requires further investigation, which would enhance our understanding of its role in cell dynamics and homeostasis.Significance of the study Our review highlighted the multifaceted cytoplasmic functions of ATM on autophagy. First, we focused on the functions of ATM in nonselective autophagy within cancer especially those induced by IR, involving the MAPK14 pathway, mTOR pathway, and Beclin1/PI3KIII complexes. These provided a theoretical understanding of tumour radiosensitivity and chemosensitivity. In addition, we emphasized the novel roles of ATM in selective autophagy, including mitophagy, pexophagy, and lipophagy. This review provides new perspectives on the importance of ATM in the diverse field of autophagy, which would provide more information on its role in whole cell dynamics and homeostasis.

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Section: Figurementioning

confidence: 99%

Multifaceted roles of ATM in autophagy: From nonselective autophagy to selective autophagy

Liang

Liu

et al. 2019

Cell Biochemistry & Function

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“…Mitophagy, selective mitochondrial degradation through autophagy, is a conserved cellular process used to eliminate damaged mitochondria. 12,13 Defective mitophagy leads to an accumulation of damaged mitochondria and exacerbates mitochondrial oxidative stress, which may shift the cell's metabolic phenotype to adapt to different pathological stimuli. [14][15][16] Our studies and others demonstrate that mitophagy/autophagy may participate in endothelial senescence, migration, and angiogenesis.…”

mentioning

confidence: 99%

Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis

Wei

Huang

Gao

et al. 2017

JAHA

107

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BackgroundEmerging evidence indicates that impaired angiogenesis may contribute to hypertension‐induced cardiac remodeling. The nicotinamide adenine dinucleotide–dependent deacetylase Sirtuin 3 (SIRT3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of this study was to examine the relationship between SIRT3‐mediated angiogenesis and cardiac remodeling.Methods and ResultsOur experiments were performed on SIRT3 knockout and age‐matched wild‐type mice infused with angiotensin II (1400 ng/kg per minute) or saline for 14 days. After angiotensin II infusion, SIRT3 knockout mice developed more severe microvascular rarefaction and functional hypoxia in cardiac tissues compared with wild‐type mice. These events were concomitant with mitochondrial dysfunction and enhanced collagen I and collagen III expression, leading to cardiac fibrosis. Silencing SIRT3 facilitated angiotensin II–induced aberrant Pink/Parkin acetylation and impaired mitophagy, while excessive mitochondrial reactive oxygen species generation limited angiogenic capacity in primary mouse cardiac microvascular endothelial cells. Moreover, SIRT3 overexpression in cardiac microvascular endothelial cells enhanced Pink/Parkin‐mediated mitophagy, attenuated mitochondrial reactive oxygen species generation, and restored vessel sprouting and tube formation. In parallel, endothelial cell–specific SIRT3 transgenic mice showed decreased fibrosis, as well as improved cardiac function and microvascular network, compared with wild‐type mice with similar stimuli.ConclusionsCollectively, these findings suggest that SIRT3 could promote angiogenesis through attenuating mitochondrial dysfunction caused by defective mitophagy.

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“…) . Here again, it was mitophagy that was specifically upregulated in ESCC cells undergoing EMT , possibly in response to increased ROS production and membrane depolarization that is known to activate Parkin‐dependent mitophagy . Inhibition of Parkin‐mediated mitophagy attenuated upregulation of CD44 and led to cell death .…”

Section: Autophagy In Tumor Stem Cells and Metastatic Dormancymentioning

confidence: 99%

Functions of autophagy in the tumor microenvironment and cancer metastasis

2018

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Macro-autophagy is an ancient and highly conserved self-degradative process that plays a homeostatic role in normal cells by eliminating organelles, pathogens, and protein aggregates. Autophagy, as it is routinely referred to, also allows cells to maintain metabolic sufficiency and survive under conditions of nutrient stress by recycling the by-products of autophagic degradation, such as fatty acids, amino acids, and nucleotides. Tumor cells are more reliant than normal cells on autophagy for survival in part due to their rapid growth rate, altered metabolism, and nutrient-deprived growth environment. How this dependence of tumor cells on autophagy affects their progression to malignancy and metastatic disease is an area of increasing research focus. Here, we review recent work identifying critical functions for autophagy in tumor cell migration and invasion, tumor stem cell maintenance and therapy resistance, and cross-talk between tumor cells and their microenvironment.

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In Brief: Mitophagy: mechanisms and role in human disease

Cited by 140 publications

References 5 publications

Multifaceted roles of ATM in autophagy: From nonselective autophagy to selective autophagy

Multifaceted roles of ATM in autophagy: From nonselective autophagy to selective autophagy

Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis

Functions of autophagy in the tumor microenvironment and cancer metastasis

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