A new CLUH to mitochondrial biogenesis

A cytosolic protein promotes mitochondrial biogenesis by binding to mRNAs encoding mitochondrial proteins, Gao et al. reveal.

CLUH is the mammalian homologue of a family of proteins that, in yeast, flies, and other organisms, regulates the morphology and distribution of mitochondria. How the proteins carry out this function, and whether CLUH plays a similar role in mammalian cells, is unknown.

Gao et al. found that CLUH mainly localized to the cytosol of mammalian cells, but small fractions of the protein appeared to associate with mitochondria and newly synthesized microtubules. In the absence of CLUH, mitochondria fragmented and clustered on one side of the nucleus, instead of forming a tubular network dispersed throughout the cell.

To learn more about CLUH’s function, the researchers looked for genes whose expression pattern in various cell types and conditions matched the expression of CLUH. Many of these coregulated genes encoded mitochondrial proteins, but others encoded proteins involved in RNA processing and translation. Gao et al. therefore wondered whether CLUH might regulate the synthesis of nuclear-encoded mitochondrial proteins. Indeed, the researchers found that CLUH bound to hundreds of mRNAs encoding mitochondrially targeted proteins, and the levels of several of these proteins were reduced in cells lacking CLUH.

Senior author Elena Rugarli thinks that CLUH might ensure that mitochondrial proteins are translated near to mitochondria so that they can be quickly imported into the organelle. She now wants to investigate whether CLUH regulates the stability, transport, or translation of its target mRNAs.