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The TORC1 signaling pathway regulates respiration-induced mitophagy in yeast.

Authors
  • Liu, Yang1
  • Okamoto, Koji2
  • 1 Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, 565-0871, Japan. , (Japan)
  • 2 Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, 565-0871, Japan. Electronic address: [email protected] , (Japan)
Type
Published Article
Journal
Biochemical and Biophysical Research Communications
Publisher
Elsevier
Publication Date
Jul 07, 2018
Volume
502
Issue
1
Pages
76–83
Identifiers
DOI: 10.1016/j.bbrc.2018.05.123
PMID: 29787763
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Mitophagy is an evolutionarily conserved autophagy process that selectively degrades mitochondria. This catabolic event is considered to be a mitochondrial quality control system crucial for cell homeostasis, however, mechanisms regulating mitophagy remain largely unknown. Here we show that the TORC1 (target of rapamycin complex 1) signaling pathway regulates mitophagy in budding yeast via SEACIT (Seh1-associated complex inhibiting TORC1) consisting of Iml1, Npr2, and Npr3. Cells lacking SEACIT displayed significant reductions in mitophagy during prolonged respiratory growth, while the other selective autophagy processes are less affected. Under the same conditions, mitophagy defects were strikingly rescued in the SEACIT mutants (1) treated with rapamycin, a specific TOR kinase inhibitor, (2) lacking Gtr1, a TORC1-stimulating Rag family GTPase downstream of SEACIT, and (3) devoid of Pib2, a phosphatidylinositol 3-phosphate-binding TORC1 activator. Notably, loss of Npr2 exacerbated mitophagy defects in cells lacking Atg13, a TORC1 effector crucial for activation of autophagy-related processes, suggesting additional mitophagy-specific regulator(s) downstream of TORC1. Finally, we found that npr2-null cells failed to stabilize the interaction of Atg32 with Atg11, a scaffold protein essential for mitophagy. Collectively, our data implicate SEACIT-mediated inactivation of TORC1 signaling as a critical step to promote respiration-induced mitophagy. Copyright © 2018 Elsevier Inc. All rights reserved.

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