Mrx4 orchestrates cytochrome b biogenesis at the yeast mitoribosomal tunnel exit

• Mitochondrial gene expression is highly regulated to ensure proper stoichiometry with imported proteins expressed from the nucleus. In yeast, one way to regulate mitochondrial translation is through feedback loops involving lowly expressed proteins called translational activators. The expression of cytochrome b (Cytb or COB), a core subunit of complex III in the respiratory chain, is regulated by five proteins called Cbp1, Cbs1, Cbs2 and Cbp3-Cbp6. All of these translational activators are needed for activation of COB translation. Here, we have identified the previously uncharacterized inner membrane protein Mrx4 as an additional regulator of Cytb biogenesis. Mrx4 interacts with the large subunit of the mitoribosome, but also with Cbp3-Cbp6 and Cbs2 as shown with crosslinking purifications. Intriguingly, deletion of MRX4 completely restores COB translation in cells devoid of Cbp3-Cbp6, indicating a repressor function of Mrx4. Further experiments using cob::ARG8 reporter strains showed that deletion of MRX4 disrupts the COB translational feedback loop, making Cbp3-Cbp6 dispensible for translation activation. We postulate that this effect is mediated by increased freedom of Cbs2 and Cbs1 to shuttle the COB mRNA to the mRNA exit site, on the mitoribosomal small subunit, and aid in translation initiation. However, disruption of the feedback loop has negative impact on the cell, as both increased levels of oxidate stress and cell death could be observed. This point to an evolutionary advantage of the feedback loop system for the yeast cell, to better adapt to changes in its environment.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

Mitochondria

mitochondrial ribosome

translation

feedback loop

protein biogenesis

biokemi

Biochemistry

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vet (ämneskategori)

ovr (ämneskategori)