MTALTND4, a second protein coded by nd4 impacts mitochondrial bioenergetics

Laura Kienzle; Stefano Bettinazzi; Marie A. Brunet; Thierry Choquette; Hajar Hosseini Khorami; Xavier Roucou; Christian R. Landry; Annie Angers; Sophie Breton

doi:10.1101/2022.04.28.489924

Molecular BiologybioRxivApr 28, 2022

Preprint

MTALTND4, a second protein coded by nd4 impacts mitochondrial bioenergetics

Laura Kienzle, Stefano Bettinazzi iD, Marie A. Brunet iD, Thierry Choquette iD, Hajar Hosseini Khorami iD, Xavier Roucou iD, Christian R. Landry iD, Annie Angers iD, Sophie Breton iD

Abstract

Recent evidence suggests that the coding potential of the mitogenome is underestimated. We found a downstream alternative ATG initiation codon in the +3 reading frame of the human mitochondrial nd4 gene. This newly characterized alternative open reading frame (altORF) encodes a 99-amino acids long polypeptide, MTALTND4, which is conserved in primates. This small protein is localized in mitochondria and cytoplasm and is also found in the plasma, and it impacts mitochondrial physiology. Alternative mitochondrial peptides such as MTALTND4 may offer a new framework for the investigation of mitochondrial functions and diseases.

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