TY - JOUR
T1 - Protease OMA1 modulates mitochondrial bioenergetics and ultrastructure through dynamic association with MICOS complex
AU - Viana, Martonio Ponte
AU - Levytskyy, Roman M.
AU - Anand, Ruchika
AU - Reichert, Andreas S.
AU - Khalimonchuk, Oleh
N1 - Funding Information:
We thank Nataliya Zahayko, Colton Roesner, and Andrew Harrahill for technical assistance and Jonathan Dietz and Dr. Iryna Bohovych for their help with gradient fractionation and native gel electrophoresis analyses; we thank Dr. Jennifer L. Fox for editorial help. Mass spectrometry analysis was performed at the Metabolomics & Proteomics Core Facility at the University of Nebraska-Lincoln, which is supported by NIH grant P30 GM103335 . We also acknowledge help form the Flow Cytometry Service Center and the Morrison Microscopy Core Facility at the University of Nebraska-Lincoln. This work was supported by NIH grants GM108975 , GM131701-01 (O.K.) and P30 GM103335 (O.K. through the Nebraska Redox Biology Center), and the Deutsche Forschungsgemeinschaft (DFG) CRC 1218 —project-ID 267205415—project B12 (A.S.R.).
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/2/19
Y1 - 2021/2/19
N2 - Remodeling of mitochondrial ultrastructure is a process that is critical for organelle physiology and apoptosis. Although the key players in this process—mitochondrial contact site and cristae junction organizing system (MICOS) and Optic Atrophy 1 (OPA1)—have been characterized, the mechanisms behind its regulation remain incompletely defined. Here, we found that in addition to its role in mitochondrial division, metallopeptidase OMA1 is required for the maintenance of intermembrane connectivity through dynamic association with MICOS. This association is independent of OPA1, mediated via the MICOS subunit MIC60, and is important for stability of MICOS and the intermembrane contacts. The OMA1-MICOS relay is required for optimal bioenergetic output and apoptosis. Loss of OMA1 affects these activities; remarkably it can be alleviated by MICOS-emulating intermembrane bridge. Thus, OMA1-dependent ultrastructure support is required for mitochondrial architecture and bioenergetics under basal and stress conditions, suggesting a previously unrecognized role for OMA1 in mitochondrial physiology.
AB - Remodeling of mitochondrial ultrastructure is a process that is critical for organelle physiology and apoptosis. Although the key players in this process—mitochondrial contact site and cristae junction organizing system (MICOS) and Optic Atrophy 1 (OPA1)—have been characterized, the mechanisms behind its regulation remain incompletely defined. Here, we found that in addition to its role in mitochondrial division, metallopeptidase OMA1 is required for the maintenance of intermembrane connectivity through dynamic association with MICOS. This association is independent of OPA1, mediated via the MICOS subunit MIC60, and is important for stability of MICOS and the intermembrane contacts. The OMA1-MICOS relay is required for optimal bioenergetic output and apoptosis. Loss of OMA1 affects these activities; remarkably it can be alleviated by MICOS-emulating intermembrane bridge. Thus, OMA1-dependent ultrastructure support is required for mitochondrial architecture and bioenergetics under basal and stress conditions, suggesting a previously unrecognized role for OMA1 in mitochondrial physiology.
KW - Cell Biology
KW - Molecular Biology
KW - Organizational Aspects of Cell Biology
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U2 - 10.1016/j.isci.2021.102119
DO - 10.1016/j.isci.2021.102119
M3 - Article
C2 - 33644718
AN - SCOPUS:85100655317
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 2
M1 - 102119
ER -