Orthogonal Persulfide Generation through Precision Tools Provides Insights into Mitochondrial Sulfane Sulfur
Suman Manna1, Ragini Agrawal2, Tarun Yadav3
1Department of Chemistry, Indian Institute of Science Education and Research Pune, Pune, Maharashtra, 411008, India.
Angewandte Chemie (International Ed. in English)
|August 2, 2024
Summary
Mitochondrial sulfane sulfur (MSS) influences human immunodeficiency virus (HIV-1) latency. This study developed tools to manipulate MSS, revealing its role in viral reactivation and host cell processes.
Area of Science:
- Biochemistry
- Cell Biology
- Virology
Background:
- The sulfane sulfur pool, including persulfides and polysulfides derived from hydrogen sulfide (H2S), is crucial in redox biochemistry.
- Mitochondria are key cellular redox hubs, but the role of endogenous mitochondrial sulfane sulfur (MSS) is understudied compared to cytosolic sulfane sulfur (CSS).
Purpose of the Study:
- To investigate the effects of endogenous mitochondrial sulfane sulfur (MSS) on cellular processes and viral latency.
- To develop novel tools for manipulating MSS levels within mitochondria.
Main Methods:
- Designed a novel artificial substrate for mitochondrial 3-mercaptopyruvate sulfurtransferase (3-MST).
- Utilized cells expressing a mitochondrion-localized persulfide biosensor to selectively enhance MSS.
- Investigated the impact of MSS on the human immunodeficiency virus (HIV-1) life cycle, including viral latency and reactivation.
Main Results:
- Demonstrated the ability of the novel tool to selectively enhance MSS in mitochondria.
- Found that MSS profoundly affects the HIV-1 life cycle, mediating viral reactivation from latency, contrasting with H2S's known suppressive effect.
- Provided evidence for the host's mitochondrial redox state, membrane potential, apoptosis, and respiration influencing HIV-1 latency and reactivation.
Conclusions:
- Dynamic fluctuations in the MSS pool significantly impact HIV-1 viral latency, potentially in conflicting ways.
- The developed precision tools enable orthogonal persulfide generation in mitochondria and cytosol, valuable for disease biology research.
Keywords:
3-Mercaptopyruvate sulfurtransferaseHIV-1Hydrogen sulfideMitochondrial sulfane sulfurRedox biologyMore Related Videos
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