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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AT 101 induces early mitochondrial dysfunction and HMOX1 (heme oxygenase 1) to trigger mitophagic cell death in glioma cells
Nina Meyer,Svenja Zielke,Jonas B. Michaelis,Benedikt Linder,Verena Warnsmann,Stefanie Rakel,Heinz D. Osiewacz,Simone Fulda,Michel Mittelbronn,Christian Münch,Christian Behrends,Donat Kögel +11 more
TL;DR: Data suggest that early mitochondrial dysfunction and HMOX1 overactivation synergize to trigger lethal mitophagy, which contributes to the cell killing effects of AT 101 in glioma cells.
Journal ArticleDOI
ZZ-dependent regulation of p62/SQSTM1 in autophagy
Yi Zhang,Su Ran Mun,Juan F. Linares,Jae-Woo Ahn,Christina G. Towers,Chang Hoon Ji,Brent E. Fitzwalter,Michael R. Holden,Wenyi Mi,Xiaobing Shi,Jorge Moscat,Andrew Thorburn,Maria T. Diaz-Meco,Yong Tae Kwon,Tatiana G. Kutateladze +14 more
TL;DR: It is shown that Nt-R binding stimulates p62 oligomerization and macroautophagy and is required for autophagic targeting of p62 and structural insights into the selective recognition of NT-R by p62ZZ are provided.
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The Unexplored Crossroads of the Female Athlete Triad and Iron Deficiency: A Narrative Review
TL;DR: How iron deficiency may interact with each component of the female athlete triad, that is, energy status, reproductive function, and bone health, is described.
Journal ArticleDOI
Targeting mitophagy in Parkinson's disease
TL;DR: The genetic evidence supporting the role for mitophagy failure as a pathogenic mechanism in Parkinson’s disease is provided and the tractability of Mitophagy pathways and prospects for drug discovery are assessed and intervention points forMitophagy enhancement are considered.
Journal ArticleDOI
Inactivation of Omi/HtrA2 protease leads to the deregulation of mitochondrial Mulan E3 ubiquitin ligase and increased mitophagy.
Lucia Cilenti,Camilla T. Ambivero,Nathan Ward,Emad S. Alnemri,Doris Germain,Antonis S. Zervos +5 more
TL;DR: A new stress-signaling pathway that is initiated in the mitochondria and involves the regulation of Mulan by Omi/HtrA2 protease is described and could be responsible for the motor neuron disease and the premature aging phenotype observed in these animals.
References
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Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
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