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

Manna, S and Agrawal, R and Yadav, T and Kumar, TA and Kumari, P and Dalai, A and Kanade, S and Balasubramanian, N and Singh, A and Chakrapani, H (2024) Orthogonal Persulfide Generation through Precision Tools Provides Insights into Mitochondrial Sulfane Sulfur. In: Angewandte Chemie - International Edition .

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Abstract

The sulfane sulfur pool, comprised of persulfide (RS-SH) and polysulfide (RS-SnH) derived from hydrogen sulfide (H2S), 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 H2S 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.

Item Type:	Journal Article
Publication:	Angewandte Chemie - International Edition
Publisher:	John Wiley and Sons Inc
Additional Information:	The copyright for this article belongs to the publisher.
Keywords:	Cell death; Hydrogen sulfide, 3-mercaptopyruvate sulfurtransferase; Cellular redox; Cytosolic; Energy generations; HIV-1; Mitochondrial sulfane sulphur; Mitochondrias; Polysulphides; Precision tools; Redox biology, Mitochondria
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	26 Oct 2024 06:24
Last Modified:	26 Oct 2024 06:24
URI:	http://eprints.iisc.ac.in/id/eprint/86554

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