Orthogonal Persulfide Generation through Precision Tools Provides Insights into Mitochondrial Sulfane Sulfur.

Autor: Manna S; Department of Chemistry, Indian Institute of Science Education and Research Pune, Pune, Maharashtra, 411008, India., Agrawal R; Department of Microbiology and Cell Biology, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, Karnataka, 560012, India., Yadav T; Department of Biology, Indian Institute of Science Education and Research Pune, Pune, Maharashtra, 411008, India., Kumar TA; Department of Chemistry, Indian Institute of Science Education and Research Pune, Pune, Maharashtra, 411008, India., Kumari P; Department of Chemistry, Indian Institute of Science Education and Research Pune, Pune, Maharashtra, 411008, India., Dalai A; Department of Biology, Indian Institute of Science Education and Research Pune, Pune, Maharashtra, 411008, India., Kanade S; Department of Biology, Indian Institute of Science Education and Research Pune, Pune, Maharashtra, 411008, India., Balasubramanian N; Department of Biology, Indian Institute of Science Education and Research Pune, Pune, Maharashtra, 411008, India., Singh A; Department of Microbiology and Cell Biology, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, Karnataka, 560012, India., Chakrapani H; Department of Chemistry, Indian Institute of Science Education and Research Pune, Pune, Maharashtra, 411008, India.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Nov 11; Vol. 63 (46), pp. e202411133. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1002/anie.202411133
Abstrakt: The sulfane sulfur pool, comprised of persulfide (RS-SH) and polysulfide (RS-S n H) derived from hydrogen sulfide (H 2 S), has emerged as a major player in redox biochemistry. Mitochondria, besides energy generation, serve as significant cellular redox hubs, mediate stress response and cellular health. However, the effects of endogenous mitochondrial sulfane sulfur (MSS) remain largely uncharacterized as compared with their cytosolic counterparts, cytosolic sulfane sulfur (CSS). To investigate this, we designed a novel artificial substrate for mitochondrial 3-mercaptopyruvate sulfurtransferase (3-MST), a key enzyme involved in MSS biosynthesis. Using cells expressing a mitochondrion-localized persulfide biosensor, we demonstrate this tool's ability to selectively enhance MSS. While H 2 S was previously known to suppress human immunodeficiency virus (HIV-1), we found that MSS profoundly affected the HIV-1 life cycle, mediating viral reactivation from latency. Additionally, we provide evidence for the role of the host's mitochondrial redox state, membrane potential, apoptosis, and respiration rates in managing HIV-1 latency and reactivation. Together, dynamic fluctuations in the MSS pool have a significant and possibly conflicting effect on HIV-1 viral latency. The precision tools developed herein allow for orthogonal generation of persulfide within both mitochondria and the cytosol and will be useful in interrogating disease biology.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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