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

## TL;DR

This study shows how Clu/Clu1 proteins form granules near mitochondria to control the production of mitochondrial proteins during metabolic changes.

## Contribution

The study reveals that Clu/Clu1 proteins regulate mitochondrial protein translation via ribosome interactions during metabolic transitions.

## Key findings

- Clu/Clu1 proteins form dynamic, membraneless granules near mitochondria in response to metabolic changes.
- Clu1 regulates translation of nuclear-encoded mitochondrial proteins by interacting with mRNAs and polysomes.
- The regulation by Clu1 occurs regardless of whether it is in a granular or diffuse state.

## 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.

Mitochondria are essential cellular organelles that perform many important roles in regulating metabolism. They are dynamic in form, function and composition which is crucial to maintain highly energy-demanding tissues. However, the factors that coordinate the proteomic changes and how they are regulated remain unclear. Here, we show that the orthologous RNA-binding proteins Clu1 (in yeast) and Clu (in Drosophila) form dynamic, membraneless, mRNA-containing granules adjacent to mitochondria under changing metabolic conditions. 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. Interestingly, this appears to be independent of whether it is in a diffuse or granular state. Our results demonstrate 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.