Mitochondrial integrity modulates mTOR signaling and podocyte function.

ABSTRACT: Mitochondrial dysfunction has emerged as a key contributor to the pathogenesis of steroid-resistant nephrotic syndrome (SRNS) and genetic focal-segmental glomerulosclerosis (FSGS). This study explores the role of mitochondrial integrity in podocyte biology, focusing on the impact of OMA1, a critical regulator of mitochondrial morphology. Using a model of disrupted mitochondrial homeostasis, we show that mitochondrial dysfunction sensitizes podocytes to insulin, triggering the overactivation of mTOR signaling. Disruption of OMA1 function was achieved through the deletion of Oma1 or a podocyte-specific knockout of its regulator Phb2. Remarkably, simultaneous Oma1 deletion extended the lifespan of severely affected Phb2 ^pko mice, alleviated proteinuria,

SUBMITTER: Ozel C 

PROVIDER: S-EPMC12774701 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature