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Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions.

Created on 08 Jul 2025

Authors

Leonor Miller-Fleming, Wing Hei Au, Laura Raik, Pedro Rebelo-Guiomar, Jasper Schmitz, Ha Yoon Cho, Aron Czako, Alexander J Whitworth

Published in

PLoS genetics. Volume 21. Issue 7. Pages e1011773. Jul 07, 2025. Epub Jul 07, 2025.

Abstract

Mitochondria perform essential metabolic functions and respond rapidly to changes in metabolic and stress conditions. As the majority of mitochondrial proteins are nuclear-encoded, intricate post-transcriptional regulation is crucial to enable mitochondria to adapt to changing cellular demands. The eukaryotic Clustered mitochondria protein family has emerged as an important regulator of mitochondrial function during metabolic shifts. Here, we show that the Drosophila melanogaster and Saccharomyces cerevisiae Clu/Clu1 proteins form dynamic, membraneless, mRNA-containing granules adjacent to mitochondria in response to metabolic changes. Yeast Clu1 regulates the translation of a subset of nuclear-encoded mitochondrial proteins by interacting with their mRNAs while these are engaged in translation. We further show that Clu1 regulates translation by interacting with polysomes, independently of whether it is in a diffuse or granular state. Our results demonstrate remarkable functional conservation with other members of the Clustered mitochondria protein family and suggest that Clu/Clu1 granules isolate and concentrate ribosomes engaged in translating their mRNA targets, thus, integrating metabolic signals with the regulation of mitochondrial protein synthesis.

PMID:
40623095
Bibliographic data and abstract were imported from PubMed on 08 Jul 2025.

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