Mitochondrial degradation and energy metabolism

Melser, Su; Lavie, Julie; Bénard, Giovanni

doi:10.1016/j.bbamcr.2015.05.010

Cited by 139 publications

(103 citation statements)

References 144 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…PINK1 and PARK2 cooperate to promote selective degradation of damaged mitochondria via mitophagy [37]. PINK1 recruits PARK2 from the cytoplasm to damaged mitochondria and subsequently promotes autophagy of the damaged mitochondria [13].…”

Section: Discussionmentioning

confidence: 99%

Polyphyllin I induces mitophagic and apoptotic cell death in human breast cancer cells by increasing mitochondrial PINK1 levels

Shen

et al. 2017

Oncotarget

View full text Add to dashboard Cite

The molecular mechanisms underlying the anti-breast cancer effects of polyphyllin I, a natural compound extracted from Paris polyphylla rhizomes, are not fully understood. In the present study, we found that polyphyllin I induces mitochondrial translocation of DRP1 by dephosphorylating DRP1 at Ser637, leading to mitochondrial fission, cytochrome c release from mitochondria into the cytosol and, ultimately apoptosis. Polyphyllin I also increased the stabilization of full-length PINK1 at the mitochondrial surface, leading to the recruitment of PARK2, P62, ubiquitin, and LC3B-II to mitochondria and culminating in mitophagy. PINK1 knockdown markedly suppressed polyphyllin I-induced mitophagy and enhanced polyphyllin I-induced, DRP1-dependent mitochondrial fission and apoptosis. Furthermore, suppression of DRP1 by mdivi-1 or shRNA inhibited PINK1 knockdown/polyphyllin I-induced mitochondrial fragmentation and apoptosis, suggesting that PINK1 depletion leads to excessive fission and, subsequently, mitochondrial fragmentation. An in vivo study confirmed that polyphyllin I greatly inhibited tumor growth and induced apoptosis in MDA-MB-231 xenografts, and these effects were enhanced by PINK1 knockdown. These data describe the mechanism by which PINK1 contributes to polyphyllin I-induced mitophagy and apoptosis and suggest that polyphyllin I may be an effective drug for breast cancer treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Polyphyllin I induces mitophagic and apoptotic cell death in human breast cancer cells by increasing mitochondrial PINK1 levels

Shen

et al. 2017

Oncotarget

View full text Add to dashboard Cite

show abstract

“…When mitophagy fails to execute efficiently, the increased number of dysfunctional mitochondria in the cell can result in programmed (apoptotic) or nonprogrammed (necrotic) cell death, and degeneration into a diseased state [Mishra and Chan, 2014;Nikoletopoulou et al, 2015]. Since healthy mitochondria do not retain PINK1 on their outer membranes [Oliveras-Salv a et al, 2014;Steer et al, 2015], upregulating the PINK1/parkin mitophagic pathways should selectively remove dysfunctional mitochondria [Palikaras and Tavernarakis, 2014;Lionaki et al, 2015;Melser et al, 2015;Wei et al, 2015] thereby affording a new and actionable therapeutic target in the treatment of AD and PD [Narendra and Youle;Lazarou et al, 2012;Ashrafi et al, 2014;Hattori et al, 2014;McLelland et al, 2014;Tufi et al, 2014;Frake et al, 2015;Kazlauskaite and Muqit, 2015;Kroemer, 2015;Pickrell and Youle, 2015;Strappazzon et al, 2015].…”

Section: Apoptotic Priming In Mitochondriamentioning

confidence: 98%

Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases

Irwin

Moos

Faller

et al. 2016

Drug Development Research

View full text Add to dashboard Cite

Preclinical Research In this review, we discuss epigenetic-driven methods for treating neurodegenerative disorders associated with mitochondrial dysfunction, focusing on carnitinoid antioxidant-histone deacetylase inhibitors that show an ability to reinvigorate synaptic plasticity and protect against neuromotor decline in vivo. Aging remains a major risk factor in patients who progress to dementia, a clinical syndrome typified by decreased mental capacity, including impairments in memory, language skills, and executive function. Energy metabolism and mitochondrial dysfunction are viewed as determinants in the aging process that may afford therapeutic targets for a host of disease conditions, the brain being primary in such thinking. Mitochondrial dysfunction is a core feature in the pathophysiology of both Alzheimer and Parkinson diseases and rare mitochondrial diseases. The potential of new therapies in this area extends to glaucoma and other ophthalmic disorders, migraine, Creutzfeldt-Jakob disease, post-traumatic stress disorder, systemic exertion intolerance disease, and chemotherapy-induced cognitive impairment. An emerging and hopefully more promising approach to addressing these hard-to-treat diseases leverages their sensitivity to activation of master regulators of antioxidant and cytoprotective genes, antioxidant response elements, and mitophagy. Drug Dev Res 77 : 109-123, 2016. © 2016 Wiley Periodicals, Inc.

show abstract

“…There are multiple selective pathways for mitophagy that are cue and context specific including FUNDC1 mediated hypoxia-induced mitophagy, NIX mediated mitophagy during erythroid differentiation, and PINK1/PARKIN mitophagy implicated during non-hypoxic mitochondrial damage and in neurodegenerative diseases including Parkinson’s disease and amyotrophic lateral sclerosis (ALS)[15,60,64,106–108] (Table 1 and 2). Through a series of elegant biochemical and cell biological studies, the molecular mechanisms of PINK1/PARKIN mediated mitophagy have recently become clear[60,61].…”

Section: Pink1/parkin Mediated Mitophagymentioning

confidence: 99%

Mechanisms of Selective Autophagy in Normal Physiology and Cancer

Mancias

Kimmelman

2016

Journal of Molecular Biology

163

123

View full text Add to dashboard Cite

Selective autophagy is critical for regulating cellular homeostasis by mediating lysosomal turnover of a wide variety of substrates including proteins, aggregates, organelles, and pathogens via a growing class of molecules termed selective autophagy receptors. The molecular mechanisms of selective autophagy receptor action and regulation are complex. Selective autophagy receptors link their bound cargo to the autophagosomal membrane by interacting with lipidated ATG8 proteins (LC3/GABARAP) that are intimately associated with the autophagosome membrane. The cargo signals that selective autophagy receptors recognize are diverse but their recognition can be broadly grouped into two classes, ubiquitin-dependent cargo recognition versus ubiquitin-independent. The roles of post-translational modification of selective autophagy receptors in regulating these pathways in response to stimuli are an active area of research. Here we will review recent advances in the identification of selective autophagy receptors and their regulatory mechanisms. Given its importance in maintaining cellular homeostasis, disruption of autophagy can lead to disease including neurodegeneration and cancer. The role of autophagy in cancer is complex as autophagy can mediate promotion or inhibition of tumorigenesis. Here we will also review the importance of autophagy in cancer with a specific focus on the role of selective autophagy receptors.

show abstract

Mitochondrial degradation and energy metabolism

Cited by 139 publications

References 144 publications

Polyphyllin I induces mitophagic and apoptotic cell death in human breast cancer cells by increasing mitochondrial PINK1 levels

Polyphyllin I induces mitophagic and apoptotic cell death in human breast cancer cells by increasing mitochondrial PINK1 levels

Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases

Mechanisms of Selective Autophagy in Normal Physiology and Cancer

Contact Info

Product

Resources

About