AbstractMitochondrial protein import is one of the key processes during mitochondrial biogenesis that involves a series of events necessary for recognition and delivery of nucleus-encoded/cytosol-synthesized mitochondrial proteins into the organelle. The past research efforts have mainly unraveled how membrane translocases ensure the correct protein sorting within the different mitochondrial subcompartments. However, early steps of recognition and delivery remain relatively uncharacterized. In this review, we discuss our current understanding about the signals on mitochondrial proteins, as well as in the mRNAs encoding them, which with the help of cytosolic chaperones and membrane receptors support protein targeting to the organelle in order to avoid improper localization. In addition, we discuss recent findings that illustrate how mistargeting of mitochondrial proteins triggers stress responses, aiming to restore cellular homeostasis.

The mitochondrial proteome is mostly composed of nuclear-encoded proteins. Such polypeptides are synthesized with signals that guide their intracellular transport to the surface of the organelle and later within the different mitochondrial subcompartments until they reach their functional destination. It has been suggested that the nascent-polypeptide associated complex (NAC) - a cytosolic chaperone that recognizes nascent chains on translationally active ribosomes - has a role in the import of nuclear-encoded mitochondrial proteins. However, the molecular mechanisms that regulate the NAC-mediated cotranslational import are still not clear. Here, we show that a particular NAC heterodimer formed by subunits α and β' in Saccharomyces cerevisiae is specifically involved in the process of mitochondrial import and functionally cooperates with Sam37, an outer membrane protein subunit of the sorting and assembly machinery complex. Mutants in both components display growth defects, incorrectly accumulate precursor forms of mitochondrial proteins in the cytosol, and have an altered mitochondrial protein content. We propose that αβ'-NAC and Sam37 are members of the system that recognizes mitochondrial proteins at early stages of their synthesis, escorting them to the import machinery of mitochondria.

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Las mitocondrias son organelos fascinantes, no solo porque son el sitio en donde se genera la energía de las células, sino por su relevancia en procesos y patologías de interés médico. La gran mayoría de las proteínas que constituyen el proteoma mitocondrial están codificadas en el núcleo y se traducen por ribosomas citosólicos, por lo que deben ser identificadas correctamente para ser distribuidas e insertadas en cada uno de los subcompartimentos mitocondriales. En este artículo realizamos una descripción de las las maquinarias de importación mitocondrial, además de las diferentes respuestas celulares que contrarrestan las alteraciones en los procesos de transporte de las proteínas o cuando existe una disfunción mitocondrial. Finalmente, mencionamos las enfermedades causadas por mutaciones en los complejos transportadores y de distribución de las proteínas de este organelo, que se han identificado hasta la fecha.