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Cited by 14Mitochondrial Function and PathologyAutophagy in Disease and TherapyATP Synthase and ATPases Research

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Identification of SLC25A46 interaction interfaces with mitochondrial membrane fusogens Opa1 and Mfn2

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Boopathy, Sivakumar, Luce, Bridget E., Lugo, Camila Makhlouta, Hakim, Pusparanee, McDonald, Julie, Kim, Ha Lin, Ponce, Jackeline, Ueberheide, Beatrix M., Chao, Luke H.·2024·Journal of Biological Chemistry
DOI 10.1016/j.jbc.2024.107740PMC PMC11459905

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Abstract

Mitochondrial fusion requires the sequential merger of four bilayers to two. The outer-membrane solute carrier protein SLC25A46 interacts with both the outer and inner-membrane dynamin family GTPases Mfn1/2 and Opa1. While SLC25A46 levels are known to affect mitochondrial morphology, how SLC25A46 interacts with Mfn1/2 and Opa1 to regulate membrane fusion is not understood. In this study, we use crosslinking mass-spectrometry and AlphaFold 2 modeling to identify interfaces mediating a SLC25A46 interactions with Opa1 and Mfn2. We reveal that the bundle signaling element of Opa1 interacts with SLC25A46, and present evidence of a Mfn2 interaction involving the SLC25A46 cytosolic face. We validate these newly identified interaction interfaces and show that they play a role in mitochondrial network maintenance.

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Metadata

Authors
Boopathy, S., Luce, B. E., Lugo, C. M., Hakim, P., McDonald, J., Kim, H. L., Ponce, J., Ueberheide, B. M., & Chao, L. H.
Affiliations
  • Harvard University (US)
  • Massachusetts General Hospital (US)
  • NYU Langone Health (US)
Corresponding author
Chao, Luke H.
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2024-10
Volume
300
Issue
10
Pages
107740
ISSN
0021-9258 (ISSN-L)
DOI
10.1016/j.jbc.2024.107740
PMC
PMC11459905
OpenAlex
W4402083452
Cited by
14
References
1
Citations by year
2026: 5 · 2025: 9
FWCI
1.91
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • National Institutes of Health (1S10OD010582-01A1)
  • NIGMS (R35GM142553)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
Keywords
SLC25A46, OPA1, mitofusin 2, mitochondrial fusion, protein-protein interfaces, mitochondrial membrane, mitochondrial morphology, cross-linking mass spectrometry

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