Loss of iron triggers PINK1/Parkin‐independent mitophagy
TLDR
A mitophagy pathway is identified and characterized, the induction of which could prove beneficial as a potential therapy for several neurodegenerative diseases in which mitochondrial clearance is advantageous.Abstract:
In this study, we develop a simple assay to identify mitophagy inducers on the basis of the use of fluorescently tagged mitochondria that undergo a colour change on lysosomal delivery. Using this assay, we identify iron chelators as a family of compounds that generate a strong mitophagy response. Iron chelation-induced mitophagy requires that cells undergo glycolysis, but does not require PINK1 stabilization or Parkin activation, and occurs in primary human fibroblasts as well as those isolated from a Parkinson's patient with Parkin mutations. Thus, we have identified and characterized a mitophagy pathway, the induction of which could prove beneficial as a potential therapy for several neurodegenerative diseases in which mitochondrial clearance is advantageous.read more
Citations
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AMPK activation induces mitophagy and promotes mitochondrial fission while activating TBK1 in a PINK1-Parkin independent manner.
Alex P. Seabright,Nicholas H. F. Fine,Jonathan Barlow,Samuel O. Lord,Ibrahim Musa,Alexander Gray,Jack A. Bryant,Manuel Banzhaf,Gareth G. Lavery,Gareth G. Lavery,D. Grahame Hardie,David J. Hodson,David J. Hodson,Andrew Philp,Andrew Philp,Yu-Chiang Lai +15 more
TL;DR: AMPK activation promotes mitophagy by enhancing mitochondrial fission (via MFF phosphorylation) and autophagosomal engulfment (via TBK1 activation) in a PINK1‐Parkin independent manner.
Journal ArticleDOI
Loss of the selective autophagy receptor p62 impairs murine myeloid leukemia progression and mitophagy
Shabnam Shaid,Shabnam Shaid,Olesya Vakhrusheva,Sebastian Koschade,Kevin Klann,Marlyn Thölken,Fatima Baker,Fatima Baker,Jing Zhang,Thomas Oellerich,Thomas Oellerich,Thomas Oellerich,Duran Sürün,Anja Derlet,Isabella Haberbosch,Stefan Eimer,Heinz D. Osiewacz,Christian Behrends,Christian Behrends,Christian Münch,Ivan Dikic,Ivan Dikic,Christian Brandts,Christian Brandts +23 more
TL;DR: It is demonstrated that the autophagy-dependent function of p62 is essential for cell growth and effective mitochondrial degradation by mitophagy, highlighting the prominent role of selective autophagic in leukemia progression, and specifically, the importance ofMitophagy to maintain mitochondrial integrity.
Journal ArticleDOI
Current Perspective of Mitochondrial Biology in Parkinson's Disease
TL;DR: How familial PD-linked genes and environmental factors interface the pathways regulating mitochondrial functions and thereby potentially converge both familial and sporadic PD at the level of mitochondrial integrity is discussed.
Journal ArticleDOI
Genes associated with Parkinson's disease: regulation of autophagy and beyond.
TL;DR: The relationships between protein products of PD genes are discussed and it is shown that common links include regulation of the autophagy–lysosome system, an important way by which cells recycle proteins and organelles.
Journal ArticleDOI
Proinflammatory NFkB signalling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading.
TL;DR: It is indicated that sustained oversupply of metabolic fuel to skeletal muscle cells induces heightened NFkB signalling and that this serves as a critical driver for disturbances in mitochondrial function and morphology, redox status, and insulin signalling.
References
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Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
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