CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins

Jie Gao, Désirée Schatton, Paola Martinelli, Henriette Hansen, David Pla-Martin, Esther Barth, Christian Becker, Janine Altmueller, Peter Frommolt, Marco Sardiello, Elena I. Rugarli

Research output: Contribution to journalArticle

Abstract

Mitochondrial function requires coordination of two genomes for protein biogenesis, efficient quality control mechanisms, and appropriate distribution of the organelles within the cell. How these mechanisms are integrated is currently not understood. Loss of the Clu1/CluA homologue (CLUH) gene led to clustering of the mitochondrial network by an unknown mechanism. We find that CLUH is coregulated both with genes encoding mitochondrial proteins and with genes involved in ribosomal biogenesis and translation. Our functional analysis identifies CLUH as a cytosolic messenger ribonucleic acid (RNA; mRNA)-binding protein. RNA immunoprecipitation experiments followed by nextgeneration sequencing demonstrated that CLUH specifically binds a subset of mRNAs encoding mitochondrial proteins. CLUH depletion decreased the levels of proteins translated by target transcripts and caused mitochondrial clustering. A fraction of CLUH colocalizes with tyrosinated tubulin and can be detected close to mitochondria, suggesting a role in regulating transport or translation of target transcripts close to mitochondria. Our data unravel a novel mechanism linking mitochondrial biogenesis and distribution.

Original languageEnglish
Pages (from-to)213-223
Number of pages11
JournalJournal of Cell Biology
Volume207
Issue number2
DOIs
StatePublished - 2014

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    Gao, J., Schatton, D., Martinelli, P., Hansen, H., Pla-Martin, D., Barth, E., Becker, C., Altmueller, J., Frommolt, P., Sardiello, M., & Rugarli, E. I. (2014). CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins. Journal of Cell Biology, 207(2), 213-223. https://doi.org/10.1083/jcb.201403129