Ecm19 coordinates mitochondrial fission and cellular redox homeostasis

Mitochondrial dynamics are tightly coupled with cellular redox homeostasis; however, the underlying regulatory mechanisms remain poorly defined. We constructed yeast mutants and evaluated mitochondrial function, morphology, and redox states using growth assays, fluorescence imaging, and flow cytometry. RNA sequencing, RIP assays, and RT-qPCR were applied to identify Ecm19p target genes. Deletion of <i>ECM19</i> alone had no evident impact on mitochondrial morphology or respiratory function. In contrast, double deletion of <i>ECM19</i> with the fusion gene <i>FZO1</i> (<i>ecm19D fzo1D</i>) rescued mitochondrial function and morphology and reduced ROS and malondialdehyde levels relative to <i>fzo1D</i>. Conversely, combining <i>ecm19D</i> with fission genes <i>MDV1</i> or <i>CAF4</i> resulted in hyperfused mitochondria, dependent on the division factor Dnm1p. RNA-seq revealed that <i>ecm19D</i> upregulates redox processes, including catalase (<i>CTA1</i>) and thiol peroxidase (<i>TSA2</i>). RIP-PCR confirmed Ecm19p binds directly to <i>CTA1</i> and <i>TSA2</i> transcripts and reduces their mRNA stability. Under H₂O₂ stress, <i>ecm19D cta1D</i> and <i>ecm19D tsa2D</i> double mutants exhibited improved growth, elevated antioxidant capacity, and lower ROS and malondialdehyde than single mutants. Ecm19 collaborates with Mdv1 and Caf4 to promote mitochondrial fission and post-transcriptionally represses <i>CTA1</i> and <i>TSA2</i> expression to regulate cellular redox, thereby coordinating mitochondrial fission with redox homeostasis.