The role of Zuo1 in mitoprotein-induced stress

Abstract

Mitochondria are essential organelles in almost all eukaryotic cells. They are the powerhouses of the cell, in charge of the production of ATP. In addition, they are also involved in calcium signaling, immune responses, and programmed cell death (apoptosis), all while producing reactive oxygen species (ROS). Their dysfunction can lead to various diseases and aging effects. There are more than 1000 different proteins in mitochondria, with 99% of them encoded by the nuclear genome. They are translated by cytosolic ribosomes, transported to and finally imported into mitochondria. The ribosome-associated complex (RAC) is required for cotranslational folding, chaperone coordination, protein quality control and stress response. It consists of an Hsp40 family protein (Zuo1) and a non-typical Hsp70 family protein (Ssz1) in yeast. This study mainly focuses on: (1) How does Zuo1 influence the biogenesis of mitochondrial outer membrane proteins? (2) What are the potential genetic interactions between Zuo1 and the mitochondrial protein import receptors Tom70/Tom71 under normal and heat stress conditions? To address these questions, I analyzed yeast cells that harbor single or multiple deletions in the genes of interest, namely ZUO1, TOM70 and/or TOM71. The results mainly demonstrated that: First, the absence of Zuo1 affects growth differently under normal and heat-stress conditions when Tom70 and Tom71 are lost. Second, the absence of Zuo1 changes the proteostasis of cells lacking Tom70/71. This study introduces a novel paradigm in which RAC functions as a stress-controlled regulatory component of the cytosolic translation machinery.