Abstract
In response to stress, cells globally shut down and reprogram cytosolic translation to adapt accordingly. Mitochondrial translation is also inhibited, but the underlying mechanisms remain unknown. Here, we analyzed the differential mitoribosome-interacting proteome in yeast cells untreated or treated with hydrogen peroxide to uncover the mitochondrial translation response to oxidative stress. The most differentially accumulated protein is the nuclear/cytosolic ATP-dependent DEADbox RNA helicase Dbp2. We show that a fraction of Dbp2 translocates to mitochondria in an Hsp42-dependent manner. In mitochondria, the low complexity domain (LCD) of Dbp2 is required for its negative-regulatory role on mitochondrial translation and cooperates with canonical mitochondrial proteins to modulate the sequestration of mitoribosome subunits and translation factors in phase-separated droplets. Together with cytosolic protein synthesis regulation, Dbp2-mediated mitochondrial translation control during stress facilitates metabolic adaptation and cell survival.