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Mitochondrial IntegrityMitochondrial Integrity Modulates mTOR Signaling and Podocyte Function 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 overactivation of mTOR signaling. Disruption of OMA1 function was achieved through deletion of Oma1 or a podocyte-specific knockout of its regulator Phb2. Remarkably, simultaneous Oma1 deletion extended the lifespan of severely affected Phb2pko mice, alleviated proteinuria, and restored mitochondrial morphology. Increased mTOR activity was observed in Phb2pko, Oma1del, and Phb2/Oma1 double-knockout mice. Our findings highlight the critical role of mitochondrial integrity in podocyte function and disease mitigation, providing potential therapeutic insights for mitochondrial dysfunction-associated nephropathies.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Renal Glomerular Capsule, Renal Glomerulus

SUBMITTER: Prerana Wagle

LAB HEAD: Paul Brinkkoetter

PROVIDER: PXD071171 | Pride | 2025-11-26

REPOSITORIES: Pride

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			Action	DRS
	20181113_Q1_AWH_ColID_726_ProjID_1496_Benzing_sample_1.raw	Raw
	20181113_Q1_AWH_ColID_726_ProjID_1496_Benzing_sample_10.raw	Raw
	20181113_Q1_AWH_ColID_726_ProjID_1496_Benzing_sample_11.raw	Raw
	20181113_Q1_AWH_ColID_726_ProjID_1496_Benzing_sample_12.raw	Raw
	20181113_Q1_AWH_ColID_726_ProjID_1496_Benzing_sample_13.raw	Raw

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