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Author Spotlight: Unveiling Oxidative Phosphorylation System Dynamics and Mitochondrial Roles in Health and Disease
Published on: May 3, 2024
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H2S remodels mitochondrial ultrastructure and destabilizes respiratory supercomplexes
David A Hanna1, Brandon Chen2, Yatrik M Shah3
1Department of Biological Chemistry, Michigan Medicine, Ann Arbor, Michigan, USA.
The Journal of Biological Chemistry
|March 22, 2025
Summary
Chronic exposure to hydrogen sulfide in colon cells disrupts mitochondrial structure and function by reducing key proteins, leading to impaired energy production. This highlights sulfide
Area of Science:
- Mitochondrial biology
- Cellular metabolism
- Gastrointestinal physiology
Background:
- Mitochondrial form and function are dynamically regulated by cellular conditions.
- Hydrogen sulfide (H2S) has complex roles in cellular respiration, acting as both a substrate and inhibitor.
- High luminal sulfide concentrations in the colon are linked to microbial activity.
Purpose of the Study:
- To investigate the impact of chronic sulfide exposure on colonocyte mitochondrial dynamics.
- To elucidate the molecular mechanisms underlying sulfide-induced mitochondrial alterations.
Main Methods:
- Exposure of colonocyte-derived cells to sulfide.
- Analysis of mitochondrial protein expression (Mic60, Mic19, Opa1).
- Assessment of mitochondrial morphology, networking, and inner membrane potential.
- Measurement of respiratory chain complex activities (CI, CIV).
Main Results:
- Chronic sulfide exposure reduced Mic60 and Mic19 expression.
- Observed significant loss of mitochondrial cristae and reduced mitochondrial networking.
- Sulfide-induced inner mitochondrial membrane depolarization activated Oma1-dependent Opa1 cleavage.
- Demonstrated profound loss of respiratory chain complex I (CI) and complex IV (CIV) activities.
Conclusions:
- Hydrogen sulfide acts as an endogenous modulator of mitochondrial dynamics in colonocytes.
- Sulfide-induced mitochondrial dysfunction involves impaired cristae structure and respiratory chain activity.
- Disrupted sulfide regulation of mitochondrial dynamics may contribute to diseases with elevated sulfide levels.
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