Open AccessThe cardiac-enriched microprotein mitolamban regulates mitochondrial respiratory complex assembly and function in mice
Author(s) -
Catherine A. Makarewich,
Amir Z. Munir,
Svetlana Bezprozvannaya,
Aaron M. Gibson,
Soo Young Kim,
Misty S. Martin-Sandoval,
Thomas P. Mathews,
Luke I. Szweda,
Rhonda BasselDuby,
Eric N. Olson
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2120476119
Subject(s) - function (biology) , biology , microbiology and biotechnology , mitochondrion , andrology , medicine
Significance Microproteins are a growing class of versatile small proteins previously overlooked by standard gene annotation methods due to their small size. Here we characterize mitolamban as a cardiac-enriched inner mitochondrial membrane–localized microprotein, which interacts with complex III of the electron transport chain and contributes to complex III assembly and function. Mitolamban gene deletion in mice leads to a reduction in complex III activity and metabolic perturbations in the heart that are consistent with complex III deficiency, as well as altered complex III assembly into respiratory supercomplexes. These findings define a functional role for mitolamban in the heart and highlight the importance of microproteins in regulating mitochondrial function and cardiomyocyte biology.