SAMM50 acts with p62 in piecemeal basal- and OXPHOS-induced mitophagy of SAM and MICOS components

Yakubu Princely Abudu; Birendra Kumar Shrestha; Wenxin Zhang; Anthimi Palara; Hanne Britt Brenne; Kenneth Bowitz Larsen; Deanna Lynn Wolfson; Gianina Dumitriu; Cristina Ionica Øie; Balpreet Singh Ahluwalia; Gahl Levy; Christian Behrends; Sharon A Tooze; Stephane Mouilleron; Trond Lamark; Terje Johansen

doi:10.1083/jcb.202009092

SAMM50 acts with p62 in piecemeal basal- and OXPHOS-induced mitophagy of SAM and MICOS components

J Cell Biol. 2021 Aug 2;220(8):e202009092. doi: 10.1083/jcb.202009092. Epub 2021 May 26.

Authors

Yakubu Princely Abudu¹, Birendra Kumar Shrestha¹, Wenxin Zhang², Anthimi Palara¹, Hanne Britt Brenne¹, Kenneth Bowitz Larsen¹, Deanna Lynn Wolfson³, Gianina Dumitriu⁴, Cristina Ionica Øie⁴, Balpreet Singh Ahluwalia³, Gahl Levy⁴, Christian Behrends^{5

6}, Sharon A Tooze², Stephane Mouilleron⁷, Trond Lamark¹, Terje Johansen¹

Affiliations

¹ Molecular Cancer Research Group, Department of Medical Biology, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.
² Molecular Cell Biology of Autophagy Laboratory, The Francis Crick Institute, London, UK.
³ Department of Physics and Technology, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.
⁴ Vascular Biology Research Group, Department of Medical Biology, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.
⁵ Institute of Biochemistry II, Goethe University Hospital, Frankfurt am Main, Germany.
⁶ Munich Cluster for Systems Neurology (SyNergy), Ludwig Maximilian University, Munich, Germany.
⁷ Structural Biology Science Technology Platform, The Francis Crick Institute, London, UK.

Abstract

Mitophagy is the degradation of surplus or damaged mitochondria by autophagy. In addition to programmed and stress-induced mitophagy, basal mitophagy processes exert organelle quality control. Here, we show that the sorting and assembly machinery (SAM) complex protein SAMM50 interacts directly with ATG8 family proteins and p62/SQSTM1 to act as a receptor for a basal mitophagy of components of the SAM and mitochondrial contact site and cristae organizing system (MICOS) complexes. SAMM50 regulates mitochondrial architecture by controlling formation and assembly of the MICOS complex decisive for normal cristae morphology and exerts quality control of MICOS components. To this end, SAMM50 recruits ATG8 family proteins through a canonical LIR motif and interacts with p62/SQSTM1 to mediate basal mitophagy of SAM and MICOS components. Upon metabolic switch to oxidative phosphorylation, SAMM50 and p62 cooperate to mediate efficient mitophagy.

Publication types

Research Support, Non-U.S. Gov't
Video-Audio Media

MeSH terms

Animals
Autophagy-Related Protein 8 Family / genetics
Autophagy-Related Protein 8 Family / metabolism
HEK293 Cells
HeLa Cells
Humans
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Mice
Microscopy, Confocal
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Mitochondria / genetics
Mitochondria / metabolism*
Mitochondria / ultrastructure
Mitochondrial Precursor Protein Import Complex Proteins
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism*
Mitophagy*
Oxidative Phosphorylation*
Protein Binding
Protein Interaction Domains and Motifs
Sequestosome-1 Protein / genetics
Sequestosome-1 Protein / metabolism*
Signal Transduction

Substances

Autophagy-Related Protein 8 Family
GABARAPL2 protein, human
Membrane Proteins
Mitochondrial Precursor Protein Import Complex Proteins
Mitochondrial Proteins
SAMM50 protein, human
SQSTM1 protein, human
Sequestosome-1 Protein

Abstract

Publication types

MeSH terms

Substances

Grants and funding