Mitochondrial dysfunction results in enhanced adrenal androgen production in H295R cells.

Mathis, Déborah; du Toit, Therina; Altinkilic, Emre Murat; Stojkov, Darko; Urzì, Christian; Voegel, Clarissa D; Wu, Vincen; Zamboni, Nicola; Simon, Hans-Uwe; Nuoffer, Jean-Marc; Flück, Christa E; Felser, Andrea (2024). Mitochondrial dysfunction results in enhanced adrenal androgen production in H295R cells. The journal of steroid biochemistry and molecular biology, 243(106561), p. 106561. Elsevier 10.1016/j.jsbmb.2024.106561

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The role of mitochondria in steroidogenesis is well established. However, the specific effects of mitochondrial dysfunction on androgen synthesis are not fully understood. In this study, we investigate the effects of various mitochondrial and metabolic inhibitors in H295R adrenal cells and perform a comprehensive analysis of steroid and metabolite profiling. We report that mitochondrial complex I inhibition by rotenone shifts cells toward anaerobic metabolism with a concomitant hyperandrogenic phenotype characterized by rapid stimulation of dehydroepiandrosterone (DHEA, 2h) and slower accumulation of androstenedione and testosterone (24h). Screening of metabolic inhibitors confirmed DHEA stimulation, which included mitochondrial complex III and mitochondrial pyruvate carrier inhibition. Metabolomic studies revealed truncated tricarboxylic acid cycle with an inverse correlation between citric acid and DHEA production as a common metabolic marker of hyperandrogenic inhibitors. The current study sheds light on a direct interplay between energy metabolism and androgen biosynthesis that could be further explored to identify novel molecular targets for efficient treatment of androgen excess disorders.

Item Type:

 Journal Article (Original Article)

Division/Institute:

 04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology > DCR Magnetic Resonance Spectroscopy and Methodology (AMSM)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Endocrinology/Metabolic Disorders
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie)

UniBE Contributor:

 Mathis, Déborah, Du Toit, Therina (B), Altinkiliç, Emre Murat, Stojkov, Darko, Urzì, Christian, Vögel, Clarissa, Simon, Hans-Uwe, Nuoffer, Jean-Marc, Flück Pandey, Christa Emma, Felser, Andrea Debora

Subjects:

 600 Technology > 610 Medicine & health

ISSN:

 1879-1220

Publisher:

 Elsevier

Language:

 English

Submitter:

 Pubmed Import

Date Deposited:

 19 Jun 2024 10:41

Last Modified:

 25 Aug 2024 00:15

Publisher DOI:

 10.1016/j.jsbmb.2024.106561

PubMed ID:

 38866189

Uncontrolled Keywords:

 DHEA androgen citrate mitochondrial dysfunction rotenone

BORIS DOI:

 10.48350/197798

URI:

 https://boris.unibe.ch/id/eprint/197798

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