An Essential Role for COPI in mRNA Localization to Mitochondria and Mitochondrial Function

Publication date: Available online 7 April 2016
Source:Cell Reports
Author(s): Dmitry Zabezhinsky, Boris Slobodin, Doron Rapaport, Jeffrey E. Gerst
Nuclear-encoded mRNAs encoding mitochondrial proteins (mMPs) can localize directly to the mitochondrial surface, yet how mMPs target mitochondria and whether RNA targeting contributes to protein import into mitochondria and cellular metabolism are unknown. Here, we show that the COPI vesicle coat complex is necessary for mMP localization to mitochondria and mitochondrial function. COPI inactivation leads to reduced mMP binding to COPI itself, resulting in the dissociation of mMPs from mitochondria, a reduction in mitochondrial membrane potential, a decrease in protein import in vivo and in vitro, and severe deficiencies in mitochondrial respiration. Using a model mMP (OXA1), we observed that COPI inactivation (or mutation of the potential COPI-interaction site) led to altered mRNA localization and impaired cellular respiration. Overall, COPI-mediated mMP targeting is critical for mitochondrial protein import and function, and transcript delivery to the mitochondria or endoplasmic reticulum is regulated by cis-acting RNA sequences and trans-acting proteins.

Graphical abstract

Teaser

Zabezhinsky et al. show that the vesicular transport complex COPI has additional functions in intracellular RNA trafficking. They provide evidence that COPI binds mRNAs encoding mitochondrial proteins and regulates their localization to mitochondria, enabling mitochondrial protein import, morphology, and function.


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