Universität zu Köln

Özel, Cem ORCID: 0009-0006-7091-7027, Abualia, Khawla ORCID: 0000-0002-7534-4014, Nguyen-Minh, Duc, Matin, Mahsa ORCID: 0000-0001-7954-6863, Unnersjö-Jess, David ORCID: 0000-0002-4162-0973, Höhne, Martin ORCID: 0000-0001-8698-5389, Bloch, Wilhelm, Hagmann, Henning ORCID: 0000-0002-2624-2740, Coward, Richard J.M., Brähler, Sebastian, Schermer, Bernhard ORCID: 0000-0002-5194-9000, Benzing, Thomas ORCID: 0000-0003-0512-1066, Antczak, Philipp ORCID: 0000-0001-9600-7757 and Brinkkötter, Paul T. ORCID: 0000-0002-4287-2080 (2026). Mitochondrial integrity modulates mTOR signaling and podocyte function. iScience, 29 (1). pp. 1-19. Elsevier. ISSN 2589-0042

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Abstract

[Artikel-Nr.: 114279] 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 mito- chondrial 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 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.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Özel, Cem UNSPECIFIED https://orcid.org/0009-0006-7091-7027 UNSPECIFIED Abualia, Khawla UNSPECIFIED https://orcid.org/0000-0002-7534-4014 UNSPECIFIED Nguyen-Minh, Duc UNSPECIFIED UNSPECIFIED UNSPECIFIED Matin, Mahsa UNSPECIFIED https://orcid.org/0000-0001-7954-6863 UNSPECIFIED Unnersjö-Jess, David UNSPECIFIED https://orcid.org/0000-0002-4162-0973 UNSPECIFIED Höhne, Martin UNSPECIFIED https://orcid.org/0000-0001-8698-5389 UNSPECIFIED Bloch, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Hagmann, Henning UNSPECIFIED https://orcid.org/0000-0002-2624-2740 UNSPECIFIED Coward, Richard J.M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brähler, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED https://orcid.org/0000-0002-5194-9000 UNSPECIFIED Benzing, Thomas UNSPECIFIED https://orcid.org/0000-0003-0512-1066 UNSPECIFIED Antczak, Philipp UNSPECIFIED https://orcid.org/0000-0001-9600-7757 UNSPECIFIED Brinkkötter, Paul T. UNSPECIFIED https://orcid.org/0000-0002-4287-2080 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-812770
Identification Number:	10.1016/j.isci.2025.114279
Journal or Publication Title:	iScience
Volume:	29
Number:	1
Page Range:	pp. 1-19
Number of Pages:	19
Date:	16 January 2026
Publisher:	Elsevier
ISSN:	2589-0042
Language:	English
Faculty:	Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Medicine > Innere Medizin > Klinik II für Innere Medizin - Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin
Subjects:	Medical sciences Medicine
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81277