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

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...

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Main Authors: Leonor Miller-Fleming, Wing Hei Au, Laura Raik, Pedro Rebelo-Guiomar, Jasper Schmitz, Ha Yoon Cho, Aron Czako, Alexander J Whitworth
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-07-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1011773
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author Leonor Miller-Fleming
Wing Hei Au
Laura Raik
Pedro Rebelo-Guiomar
Jasper Schmitz
Ha Yoon Cho
Aron Czako
Alexander J Whitworth
author_facet Leonor Miller-Fleming
Wing Hei Au
Laura Raik
Pedro Rebelo-Guiomar
Jasper Schmitz
Ha Yoon Cho
Aron Czako
Alexander J Whitworth
author_sort Leonor Miller-Fleming
collection DOAJ
description 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.
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institution DOAJ
issn 1553-7390
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language English
publishDate 2025-07-01
publisher Public Library of Science (PLoS)
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spelling doaj-art-d5ce4c4723b6409d8a792e3efa1139532025-08-20T03:12:57ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-07-01217e101177310.1371/journal.pgen.1011773Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions.Leonor Miller-FlemingWing Hei AuLaura RaikPedro Rebelo-GuiomarJasper SchmitzHa Yoon ChoAron CzakoAlexander J WhitworthMitochondria 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.https://doi.org/10.1371/journal.pgen.1011773
spellingShingle Leonor Miller-Fleming
Wing Hei Au
Laura Raik
Pedro Rebelo-Guiomar
Jasper Schmitz
Ha Yoon Cho
Aron Czako
Alexander J Whitworth
Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions.
PLoS Genetics
title Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions.
title_full Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions.
title_fullStr Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions.
title_full_unstemmed Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions.
title_short Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions.
title_sort clu1 clu form mitochondria associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions
url https://doi.org/10.1371/journal.pgen.1011773
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