Mitochondrial Ca2+ oscillation induces mitophagy initiation through the PINK1-Parkin pathway

Dysregulation of the PINK1/Parkin-mediated mitophagy is essential to Parkinson’s disease. Although important progress has been made in previous researches, the biochemical reagents that induce global and significant mitochondrial damage may still hinder deeper insights into the mechanisms of mitopha...

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Bibliographic Details
Published in:Cell death & disease 2021-06, Vol.12 (7), p.632-632, Article 632
Main Authors: Yu, Zhengying, Wang, Haipeng, Tang, Wanyi, Wang, Shaoyang, Tian, Xiaoying, Zhu, Yujie, He, Hao
Format: Article
Language:English
Subjects:
13/109
14/19
14/35
14/63
631/80/39/2348
631/80/86/1999
Antibodies
Apoptosis
Biochemistry
Biomedical and Life Sciences
Calcium (mitochondrial)
Calcium signalling
Cell Biology
Cell Culture
Depolarization
Efficiency
Immunology
Lasers
Life Sciences
Membrane potential
Microscopy
Mitochondria
Mitophagy
Movement disorders
Mutation
Neurodegenerative diseases
Oscillations
Parkin protein
Parkinson's disease
PTEN-induced putative kinase
Reactive oxygen species
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Summary:Dysregulation of the PINK1/Parkin-mediated mitophagy is essential to Parkinson’s disease. Although important progress has been made in previous researches, the biochemical reagents that induce global and significant mitochondrial damage may still hinder deeper insights into the mechanisms of mitophagy. The origin of PINK1/Parkin pathway activation in mitophagy remains elusive. In this study, we develop an optical method, ultra-precise laser stimulation (UPLaS) that delivers a precise and noninvasive stimulation onto a submicron region in a single mitochondrial tubular structure. UPLaS excites localized mitochondrial Ca 2+ (mitoCa 2+ ) oscillations with tiny perturbation to mitochondrial membrane potential (MMP) or mitochondrial reactive oxygen species. The UPLaS-induced mitoCa 2+ oscillations can directly induce PINK1 accumulation and Parkin recruitment on mitochondria. The Parkin recruitment by UPLaS requires PINK1. Our results provide a precise and noninvasive technology for research on mitophagy, which stimulates target mitochondria with little damage, and reveal mitoCa 2+ oscillation directly initiates the PINK1-Parkin pathway for mitophagy without MMP depolarization.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-021-03913-3