Mitophagy in neurodegeneration and aging

Fivenson, Elayne M.; Lautrup, Sofie; Sun, Nuo; Scheibye‐Knudsen, Morten; Stevnsner, Tinna; Nilsen, Hilde; Bohr, Vilhelm A.; Fang, Evandro Fei

doi:10.1016/j.neuint.2017.02.007

Cited by 274 publications

(174 citation statements)

References 111 publications

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“…Defects in mitophagy result in accumulation of dysfunctional mitochondria seen in aging and age-related disorders [9–11]. Conversely, upregulation of mitophagy successfully ameliorates mitochondrial dysfunction and cell toxicity in diseases like diabetes mellitus (DM) and Parkinson's disease [12, 13].…”

Section: Introductionmentioning

confidence: 99%

Mitophagy Transcriptome: Mechanistic Insights into Polyphenol-Mediated Mitophagy

Tan

Wong

2017

Oxidative Medicine and Cellular Longevity

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Mitochondria are important bioenergetic and signalling hubs critical for myriad cellular functions and homeostasis. Dysfunction in mitochondria is a central theme in aging and diseases. Mitophagy, a process whereby damaged mitochondria are selectively removed by autophagy, plays a key homeostatic role in mitochondrial quality control. Upregulation of mitophagy has shown to mitigate superfluous mitochondrial accumulation and toxicity to safeguard mitochondrial fitness. Hence, mitophagy is a viable target to promote longevity and prevent age-related pathologies. Current challenge in modulating mitophagy for cellular protection involves identification of physiological ways to activate the pathway. Till date, mitochondrial stress and toxins remain the most potent inducers of mitophagy. Polyphenols have recently been demonstrated to protect mitochondrial health by facilitating mitophagy, thus suggesting the exciting prospect of augmenting mitophagy through dietary intake. In this review, we will first discuss the different surveillance mechanisms responsible for the removal of damaged mitochondrial components, followed by highlighting the transcriptional regulatory mechanisms of mitophagy. Finally, we will review the functional connection between polyphenols and mitophagy and provide insight into the underlying mechanisms that potentially govern polyphenol-induced mitophagy.

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Section: Introductionmentioning

confidence: 99%

Mitophagy Transcriptome: Mechanistic Insights into Polyphenol-Mediated Mitophagy

Tan

Wong

2017

Oxidative Medicine and Cellular Longevity

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“…, cell culture conditions such as cell density, starvation, hypoxia, etc. ) 1,5,8 . Therefore, it is paramount that the same experimental conditions are maintained for all experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Mitophagy is a multiple-step process involving many proteins and protein complexes 5,7,8 . In brief, a damaged mitochondrion is first recognized and engulfed by a double-membraned phagophore, which can originate from the plasma membrane, endoplasmic reticulum, Golgi complex, nucleus, or mitochondrion itself 9 , 10 .…”

Section: Introductionmentioning

confidence: 99%

“…The spherical phagophore elongates and eventually seals the mitochondria inside, constituting the mitochondrial autophagosome (mitophagosome). The mitophagosome then fuses with the lysosome for degradation, forming an autolysosome in which the damaged mitochondrion is degraded and recycled 7, 8 . Major autophagic proteins also involved in mitophagy include: Autophagy Related 7 (ATG7) and Beclin1 (initiation), Microtubule-Associated Protein 1A/1B-Light Chain 3 (LC3-II) (LGG-1 in C. elegans) and p62 (components of phagophore), and lysosomal-associated membrane glycoprotein 2 (LAMP2) 6,7 .…”

Section: Introductionmentioning

confidence: 99%

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In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice

Fang

Palikaras

Sun

et al. 2017

JoVE

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Mitochondria are the powerhouses of cells and produce cellular energy in the form of ATP. Mitochondrial dysfunction contributes to biological aging and a wide variety of disorders including metabolic diseases, premature aging syndromes, and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Maintenance of mitochondrial health depends on mitochondrial biogenesis and the efficient clearance of dysfunctional mitochondria through mitophagy. Experimental methods to accurately detect autophagy/mitophagy, especially in animal models, have been challenging to develop. Recent progress towards the understanding of the molecular mechanisms of mitophagy has enabled the development of novel mitophagy detection techniques. Here, we introduce several versatile techniques to monitor mitophagy in human cells, Caenorhabditis elegans (e.g., Rosella and DCT-1/ LGG-1 strains), and mice (mt-Keima). A combination of these mitophagy detection techniques, including cross-species evaluation, will improve the accuracy of mitophagy measurements and lead to a better understanding of the role of mitophagy in health and disease.

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“…; and (c) overall, how does this interconnection contribute to age-associated disease phenotypes and aging? Numerous forms of endogenous and environmental stressors may disrupt mitochondrial function by impacting critical processes in mitochondrial homeostasis, such as mitochondrial redox system, oxidative phosphorylation, biogenesis, and mitophagy (Fivenson et al, 2017; Lerner et al, 2016). In this regard, it is intriguing that mitochondrial dysfunction is causally resulted from defects of DNA repair mechanisms which have been identified to accelerate aging process (Fang et al, 2014).…”

Section: Recent Advances – Mitochondrial Dysfunction/damps and Cmentioning

confidence: 99%

Mitochondrial dysfunction and damage associated molecular patterns (DAMPs) in chronic inflammatory diseases

2018

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Inflammation represents a comprehensive host response to external stimuli for the purpose of eliminating the offending agent, minimizing injury to host tissues and fostering repair of damaged tissues back to homeostatic levels. In normal physiologic context, inflammatory response culminates with the resolution of infection and tissue damage response. However, in a pathologic context, persistent or inappropriately regulated inflammation occurs that can lead to chronic inflammatory diseases. Recent scientific advances have integrated the role of innate immune response to be an important arm of the inflammatory process. Accordingly, the dysregulation of innate immunity has been increasingly recognized as a driving force of chronic inflammatory diseases. Mitochondria have recently emerged as organelles which govern fundamental cellular functions including cell proliferation or differentiation, cell death, metabolism and cellular signaling that are important in innate immunity and inflammation-mediated diseases. As a natural consequence, mitochondrial dysfunction has been highlighted in a myriad of chronic inflammatory diseases. Moreover, the similarities between mitochondrial and bacterial constituents highlight the intrinsic links in the innate immune mechanisms that control chronic inflammation in diseases where mitochondrial damage associated molecular patterns (DAMPs) have been involved. Here in this review, the role of mitochondria in innate immune responses is discussed and how it pertains to the mitochondrial dysfunction or DAMPs seen in chronic inflammatory diseases is reviewed.

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Mitophagy in neurodegeneration and aging

Cited by 274 publications

References 111 publications

Mitophagy Transcriptome: Mechanistic Insights into Polyphenol-Mediated Mitophagy

Mitophagy Transcriptome: Mechanistic Insights into Polyphenol-Mediated Mitophagy

<em>In Vitro</em> and <em>In Vivo</em> Detection of Mitophagy in Human Cells,<em> C. Elegans</em>, and Mice

Mitochondrial dysfunction and damage associated molecular patterns (DAMPs) in chronic inflammatory diseases

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