Molecular mechanisms and physiological functions of mitophagy

Degradation of mitochondria via a selective form of autophagy, named mitophagy, is a fundamental mechanism conserved from yeast to humans that regulates mitochondrial quality and quantity control. Mitophagy is promoted via specific mitochondrial outer membrane receptors, or ubiquitin molecules conju...

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Published in:The EMBO journal Vol. 40; no. 3; pp. e104705 - n/a
Main Authors: Onishi, Mashun, Yamano, Koji, Sato, Miyuki, Matsuda, Noriyuki, Okamoto, Koji
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.02.2021
Springer Nature B.V
John Wiley and Sons Inc
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ISSN:0261-4189, 1460-2075, 1460-2075
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Abstract Degradation of mitochondria via a selective form of autophagy, named mitophagy, is a fundamental mechanism conserved from yeast to humans that regulates mitochondrial quality and quantity control. Mitophagy is promoted via specific mitochondrial outer membrane receptors, or ubiquitin molecules conjugated to proteins on the mitochondrial surface leading to the formation of autophagosomes surrounding mitochondria. Mitophagy‐mediated elimination of mitochondria plays an important role in many processes including early embryonic development, cell differentiation, inflammation, and apoptosis. Recent advances in analyzing mitophagy in vivo also reveal high rates of steady‐state mitochondrial turnover in diverse cell types, highlighting the intracellular housekeeping role of mitophagy. Defects in mitophagy are associated with various pathological conditions such as neurodegeneration, heart failure, cancer, and aging, further underscoring the biological relevance. Here, we review our current molecular understanding of mitophagy, and its physiological implications, and discuss how multiple mitophagy pathways coordinately modulate mitochondrial fitness and populations. Graphical Abstract This review describes the conserved pathways for mitochondrial degradation via selective autophagy across species, and how multiple mitophagy pathways cooperate to modulate mitochondrial fitness and number in normal or disease physiology.
AbstractList Degradation of mitochondria via a selective form of autophagy, named mitophagy, is a fundamental mechanism conserved from yeast to humans that regulates mitochondrial quality and quantity control. Mitophagy is promoted via specific mitochondrial outer membrane receptors, or ubiquitin molecules conjugated to proteins on the mitochondrial surface leading to the formation of autophagosomes surrounding mitochondria. Mitophagy-mediated elimination of mitochondria plays an important role in many processes including early embryonic development, cell differentiation, inflammation, and apoptosis. Recent advances in analyzing mitophagy in vivo also reveal high rates of steady-state mitochondrial turnover in diverse cell types, highlighting the intracellular housekeeping role of mitophagy. Defects in mitophagy are associated with various pathological conditions such as neurodegeneration, heart failure, cancer, and aging, further underscoring the biological relevance. Here, we review our current molecular understanding of mitophagy, and its physiological implications, and discuss how multiple mitophagy pathways coordinately modulate mitochondrial fitness and populations.Degradation of mitochondria via a selective form of autophagy, named mitophagy, is a fundamental mechanism conserved from yeast to humans that regulates mitochondrial quality and quantity control. Mitophagy is promoted via specific mitochondrial outer membrane receptors, or ubiquitin molecules conjugated to proteins on the mitochondrial surface leading to the formation of autophagosomes surrounding mitochondria. Mitophagy-mediated elimination of mitochondria plays an important role in many processes including early embryonic development, cell differentiation, inflammation, and apoptosis. Recent advances in analyzing mitophagy in vivo also reveal high rates of steady-state mitochondrial turnover in diverse cell types, highlighting the intracellular housekeeping role of mitophagy. Defects in mitophagy are associated with various pathological conditions such as neurodegeneration, heart failure, cancer, and aging, further underscoring the biological relevance. Here, we review our current molecular understanding of mitophagy, and its physiological implications, and discuss how multiple mitophagy pathways coordinately modulate mitochondrial fitness and populations.
Degradation of mitochondria via a selective form of autophagy, named mitophagy, is a fundamental mechanism conserved from yeast to humans that regulates mitochondrial quality and quantity control. Mitophagy is promoted via specific mitochondrial outer membrane receptors, or ubiquitin molecules conjugated to proteins on the mitochondrial surface leading to the formation of autophagosomes surrounding mitochondria. Mitophagy‐mediated elimination of mitochondria plays an important role in many processes including early embryonic development, cell differentiation, inflammation, and apoptosis. Recent advances in analyzing mitophagy in vivo also reveal high rates of steady‐state mitochondrial turnover in diverse cell types, highlighting the intracellular housekeeping role of mitophagy. Defects in mitophagy are associated with various pathological conditions such as neurodegeneration, heart failure, cancer, and aging, further underscoring the biological relevance. Here, we review our current molecular understanding of mitophagy, and its physiological implications, and discuss how multiple mitophagy pathways coordinately modulate mitochondrial fitness and populations. Graphical Abstract This review describes the conserved pathways for mitochondrial degradation via selective autophagy across species, and how multiple mitophagy pathways cooperate to modulate mitochondrial fitness and number in normal or disease physiology.
Degradation of mitochondria via a selective form of autophagy, named mitophagy, is a fundamental mechanism conserved from yeast to humans that regulates mitochondrial quality and quantity control. Mitophagy is promoted via specific mitochondrial outer membrane receptors, or ubiquitin molecules conjugated to proteins on the mitochondrial surface leading to the formation of autophagosomes surrounding mitochondria. Mitophagy‐mediated elimination of mitochondria plays an important role in many processes including early embryonic development, cell differentiation, inflammation, and apoptosis. Recent advances in analyzing mitophagy in vivo also reveal high rates of steady‐state mitochondrial turnover in diverse cell types, highlighting the intracellular housekeeping role of mitophagy. Defects in mitophagy are associated with various pathological conditions such as neurodegeneration, heart failure, cancer, and aging, further underscoring the biological relevance. Here, we review our current molecular understanding of mitophagy, and its physiological implications, and discuss how multiple mitophagy pathways coordinately modulate mitochondrial fitness and populations.
Degradation of mitochondria via a selective form of autophagy, named mitophagy, is a fundamental mechanism conserved from yeast to humans that regulates mitochondrial quality and quantity control. Mitophagy is promoted via specific mitochondrial outer membrane receptors, or ubiquitin molecules conjugated to proteins on the mitochondrial surface leading to the formation of autophagosomes surrounding mitochondria. Mitophagy‐mediated elimination of mitochondria plays an important role in many processes including early embryonic development, cell differentiation, inflammation, and apoptosis. Recent advances in analyzing mitophagy in vivo also reveal high rates of steady‐state mitochondrial turnover in diverse cell types, highlighting the intracellular housekeeping role of mitophagy. Defects in mitophagy are associated with various pathological conditions such as neurodegeneration, heart failure, cancer, and aging, further underscoring the biological relevance. Here, we review our current molecular understanding of mitophagy, and its physiological implications, and discuss how multiple mitophagy pathways coordinately modulate mitochondrial fitness and populations. This review describes the conserved pathways for mitochondrial degradation via selective autophagy across species, and how multiple mitophagy pathways cooperate to modulate mitochondrial fitness and number in normal or disease physiology.
Degradation of mitochondria via a selective form of autophagy, named mitophagy, is a fundamental mechanism conserved from yeast to humans that regulates mitochondrial quality and quantity control. Mitophagy is promoted via specific mitochondrial outer membrane receptors, or ubiquitin molecules conjugated to proteins on the mitochondrial surface leading to the formation of autophagosomes surrounding mitochondria. Mitophagy‐mediated elimination of mitochondria plays an important role in many processes including early embryonic development, cell differentiation, inflammation, and apoptosis. Recent advances in analyzing mitophagy in vivo also reveal high rates of steady‐state mitochondrial turnover in diverse cell types, highlighting the intracellular housekeeping role of mitophagy. Defects in mitophagy are associated with various pathological conditions such as neurodegeneration, heart failure, cancer, and aging, further underscoring the biological relevance. Here, we review our current molecular understanding of mitophagy, and its physiological implications, and discuss how multiple mitophagy pathways coordinately modulate mitochondrial fitness and populations. This review describes the conserved pathways for mitochondrial degradation via selective autophagy across species, and how multiple mitophagy pathways cooperate to modulate mitochondrial fitness and number in normal or disease physiology.
Author Okamoto, Koji
Yamano, Koji
Onishi, Mashun
Matsuda, Noriyuki
Sato, Miyuki
AuthorAffiliation 2 The Ubiquitin Project Tokyo Metropolitan Institute of Medical Science Tokyo Japan
1 Laboratory of Mitochondrial Dynamics Graduate School of Frontier Biosciences Osaka University Suita Japan
3 Laboratory of Molecular Membrane Biology Institute for Molecular and Cellular Regulation Gunma University Maebashi Japan
AuthorAffiliation_xml – name: 1 Laboratory of Mitochondrial Dynamics Graduate School of Frontier Biosciences Osaka University Suita Japan
– name: 3 Laboratory of Molecular Membrane Biology Institute for Molecular and Cellular Regulation Gunma University Maebashi Japan
– name: 2 The Ubiquitin Project Tokyo Metropolitan Institute of Medical Science Tokyo Japan
Author_xml – sequence: 1
  givenname: Mashun
  orcidid: 0000-0003-1511-4097
  surname: Onishi
  fullname: Onishi, Mashun
  organization: Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University
– sequence: 2
  givenname: Koji
  orcidid: 0000-0002-4692-161X
  surname: Yamano
  fullname: Yamano, Koji
  organization: The Ubiquitin Project, Tokyo Metropolitan Institute of Medical Science
– sequence: 3
  givenname: Miyuki
  orcidid: 0000-0002-1944-4918
  surname: Sato
  fullname: Sato, Miyuki
  email: m-sato@gunma-u.ac.jp
  organization: Laboratory of Molecular Membrane Biology, Institute for Molecular and Cellular Regulation, Gunma University
– sequence: 4
  givenname: Noriyuki
  orcidid: 0000-0001-8199-952X
  surname: Matsuda
  fullname: Matsuda, Noriyuki
  email: matsuda-nr@igakuken.or.jp
  organization: The Ubiquitin Project, Tokyo Metropolitan Institute of Medical Science
– sequence: 5
  givenname: Koji
  orcidid: 0000-0003-4730-4522
  surname: Okamoto
  fullname: Okamoto, Koji
  email: kokamoto@fbs.osaka-u.ac.jp
  organization: Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33438778$$D View this record in MEDLINE/PubMed
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Issue 3
Keywords autophagy
phosphorylation
mitochondria
quality and quantity control
ubiquitin
Language English
License Attribution
2021 The Authors. Published under the terms of the CC BY 4.0 license.
This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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See the Glossary for abbreviations used in this article.
These authors contributed equally to this work
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Di Rita, Peschiaroli, D’Acunzo, Strobbe, Hu, Gruber, Nygaard, Lambrughi, Melino, Papaleo (CR38) 2018; 9
Nakahira, Haspel, Rathinam, Lee, Dolinay, Lam, Englert, Rabinovitch, Cernadas, Kim (CR164) 2011; 12
Kageyama, Hoshijima, Seo, Bedja, Sysa‐Shah, Andrabi, Chen, Hoke, Dawson, Dawson (CR91) 2014; 33
Song, McMackin, Nguyen, Cortopassi (CR247) 2017; 100
Hong, Liu, Zhu, Zhuang, Suo, Wang, Huang, Xu, Huang, Yu (CR79) 2014; 23
Furukawa, Fukuda, Yamashita, Saigusa, Kurihara, Yoshida, Kirisako, Nakatogawa, Kanki (CR55) 2018; 23
Ploumi, Daskalaki, Tavernarakis (CR199) 2017; 284
Xu, Li, Chen, Li, Zhao, Yao, Dong, Wen, Wang, Zhao (CR300) 2018; 14
Chandel, Jasper, Ho, Passegue (CR24) 2016; 18
Yonashiro, Ishido, Kyo, Fukuda, Goto, Matsuki, Ohmura‐Hoshino, Sada, Hotta, Yamamura (CR308) 2006; 25
Kabeya, Mizushima, Ueno, Yamamoto, Kirisako, Noda, Kominami, Ohsumi, Yoshimori (CR89) 2000; 19
Eisner, Picard, Hajnoczky (CR45) 2018; 20
Igarashi, Yamashita, Yamashita, Inoue, Fukuda, Fukuchi, Kanki (CR80
2018; 561
2016; 428
2019; 10
2017; 88
2013; 126
2016b; 133
2015; 142
2010; 189
2014a; 10
2005; 65
2020; 10
2012; 14
1998; 392
2020; 19
2013; 59
2000; 19
2019; 22
2018; 217
2013; 51
2019; 26
2013; 52
2016; 41
2019; 29
2017; 162
2017; 284
2013; 110
2002; 91
2010; 191
2010; 5
2017; 168
2012; 22
2006; 441
2010; 6
2010; 8
2014; 97
2011; 1
2010a; 12
2007; 282
1996; 93
2010; 285
2015; 1853
2017; 130
2013; 340
2016; 18
2016; 17
2011; 6
2012; 34
2004; 304
2011; 7
2016; 12
2006; 355
2007; 16
2004; 429
2014; 547
2016; 5
2011; 147
2015; 116
2005; 8
2016; 215
2016; 214
2020; 21
2019; 294
2008; 134
2016; 26
2016; 24
2006; 103
2016; 22
2004; 61
2017; 44
2010; 140
2000; 290
2013; 19
2014; 5
2013; 14
2015; 290
2013; 17
2014; 3
2017; 37
2017; 36
2013; 10
2014b; 15
2017; 38
1997; 186
2007; 130
2019; 69
2016; 113
2016; 354
2016; 353
2001; 15
2016b; 5
2014; 56
2014; 54
2009; 325
2014; 289
2011; 334
2017; 20
2014; 512
2016a; 92
2011; 333
2015; 6
2015; 5
2019; 74
2019; 76
2017; 24
2010; 362
2000; 275
2020; 77
2014; 510
2011; 108
2013; 32
2018; 559
2017; 17
2002; 23
2016a; 291
2017; 10
2017; 13
2017; 12
1999; 274
2009; 9
2017; 18
2008; 454
2017; 100
2010; 11
2007; 104
2013; 4
2010a; 139
2010; 107
2010; 19
2010; 465
2014; 26
2014; 25
2015; 309
2018; 41
2014; 29
2014; 28
2012; 125
2017; 552
2013; 5
2014; 23
2013; 9
2008; 183
2018; 7
2010; 22
2009; 11
2018; 9
2018; 8
2018; 4
2010; 29
2015; 85
2005; 105
2006; 25
2015; 87
2014; 16
1994; 79
2020; 1–12
2016; 159
2001; 412
2020; 219
2018; 37
2009; 17
2014; 124
2015; 57
2019; 8
2018; 28
2015; 521
2018; 503
2002; 6
2002; 3
2003; 37
2014; 46
2015; 524
2018; 23
2018; 20
1996; 15
2018; 27
2014; 159
2018; 25
2018; 19
2010; 42
2004; 279
2015; 60
2011; 91
2005; 123
2000; 79
2018; 11
2003; 100
2014; 33
2019; 453
2005; 12
2018; 15
2018; 14
2015; 34
2017; 6
2018; 122
2017; 7
2017; 8
2012; 287
2015; 347
2016; 76
2013; 288
2011; 12
2013; 280
2011; 18
2019; 1880
1999; 402
2005; 24
2017; 997
2014; 206
2014; 205
2004; 131
2016; 90
2015; 43
2011; 20
2011; 22
1997; 17
2011; 21
2005; 309
2009; 284
2011; 287
2010b; 285
2013; 1833
2015; 17
2015; 16
2007; 405
2015; 18
2008; 18
2020; 181
2015; 11
2000; 20
2005; 437
2017; 292
2013; 1281
2015; 209
2006; 2
2010b; 6
2014; 111
1998; 21
2001; 68
2008; 283
2015; 24
2015; 25
2012; 2
2002; 282
2012; 3
2015; 22
2013; 496
1983; 40
2013; 495
2014; 460
2004; 117
2008; 295
2012; 8
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Snippet Degradation of mitochondria via a selective form of autophagy, named mitophagy, is a fundamental mechanism conserved from yeast to humans that regulates...
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SubjectTerms Aging
Apoptosis
Autophagy
Cell differentiation
Congestive heart failure
Differentiation (biology)
EMBO07
Embryogenesis
Embryonic growth stage
Mitochondria
Mitophagy
Molecular modelling
Neurodegeneration
Phagocytosis
Phagosomes
phosphorylation
Physiology
quality and quantity control
Review
Reviews
Ubiquitin
Yeast
Title Molecular mechanisms and physiological functions of mitophagy
URI https://link.springer.com/article/10.15252/embj.2020104705
https://onlinelibrary.wiley.com/doi/abs/10.15252%2Fembj.2020104705
https://www.ncbi.nlm.nih.gov/pubmed/33438778
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https://www.proquest.com/docview/2477520431
https://pubmed.ncbi.nlm.nih.gov/PMC7849173
Volume 40
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