The Obg-like ATPase Ola1 prevents excessive mitochondrial reactive oxygen species by inhibiting MAPK/Pmk1 signaling in fission yeast

Ola1 plays critical roles in maintaining cellular homeostasis by regulating the cell cycle, translation, and heat shock responses. Additionally, it modulates antioxidant responses and redox homeostasis, processes in which mitochondria are key contributors. However, the precise mechanism by which Ola1 modules mitochondrial reactive oxygen species (mtROS) levels and the functional consequences of this regulation remain poorly understood. In this study, we demonstrate that the absence of Ola1 leads to increased mtROS levels through the modulation of the MAPK/Pmk1 signaling pathway in the fission yeast Schizosaccharomyces pombe. We further establish that Ola1 physically interacts with both MAPK/Pmk1 and its upstream kinase Pek1 (MAPKK), thereby inhibiting MAPK/Pmk1 signaling. Moreover, we show that increased mtROS levels in cells lacking Ola1 promote nuclear localization of the stress-responsive transcription factor Hsf1 and upregulate Ssa1, the fission yeast homolog of mammalian Hsp70. Therefore, our findings uncover a previously uncharacterized role of Ola1 in modulating mtROS through the MAPK/Pmk1 signaling pathway and underscore the crucial function of Ola1 in stress response and the maintenance of cellular homeostasis.