Protein kinase 2 of the giant sarcomeric protein UNC-89 regulates mitochondrial morphology and function
UNC-89 is a giant sarcomeric M-line protein required for sarcomere organization and optimal muscle function. UNC-89 contains two protein kinase domains, PK1 and PK2, separated by an elastic region. Here we show that PK2 is a canonical kinase expected to be catalytically active. C. elegans expressing UNC-89 with a lysine to alanine (KtoA) mutation to inactivate PK2 have normally organized sarcomeres and SR, and normal muscle function. PK2 KtoA mutants have fragmented mitochondria, correlated with more mitochondrially-associated DRP-1. PK2 KtoA mutants have increased ATP levels, increased glycolysis and altered levels of electron transport chain complexes. Muscle mitochondria show increased complex I and decreased complex II basal respiration, each of which cannot be uncoupled. This suggests that mutant mitochondria are already uncoupled, possibly resulting from an increased level of the uncoupling protein, UCP-4. Our results suggest signaling from sarcomeres to mitochondria, to help match energy requirements with energy production.
Authors
- Till Dorendorf (ORCID: https://orcid.org/0000-0002-8319-8010)
- Nasab Ghazal (ORCID: https://orcid.org/0000-0001-9298-3144)
- Steven Zuryn (ORCID: https://orcid.org/0000-0002-3551-6790)
- Arnaud Ahier (ORCID: https://orcid.org/0000-0002-9999-3887)
- Jennifer Q. Kwong (ORCID: https://orcid.org/0000-0001-9867-7658)
- Guy M. Benian (ORCID: https://orcid.org/0000-0002-8236-3176)
- Jasmine C. Moody (ORCID: https://orcid.org/0000-0002-0465-0647)
- Siva A. Vanapalli (ORCID: https://orcid.org/0000-0001-6036-1949)
- Hiroshi Qadota (ORCID: https://orcid.org/0000-0002-6769-9464)
- Leila Lesanpezeshki (ORCID: https://orcid.org/0000-0001-8111-4314)
- Courtney J. Matheny (ORCID: https://orcid.org/0000-0001-7707-5180)
- Olga Mayans (ORCID: https://orcid.org/0000-0001-6876-8532)
- Yohei Matsunaga
Institutions
- Texas Tech University (US)
- Emory Healthcare (US)
- Emory University (US)
- The University of Queensland (AU)
- University of Konstanz (DE)
- Park Centre for Mental Health (AU)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-10-17
- DOI
- https://doi.org/10.1038/s42003-024-07042-3
- Citations
- 2
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 0.47
Funders
- National Science Foundation
- National Aeronautics and Space Administration
- Georgia Institute of Technology
- Emory University
- Oklahoma Medical Research Foundation
- Universität Konstanz
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council