H ₂ S remodels mitochondrial ultrastructure and destabilizes respiratory supercomplexes

Area of Science:

• Cell Biology
• Mitochondrial Biology
• Metabolic Biochemistry

Background:

• Mitochondrial form and function are dynamic, responding to cellular energy needs and stress.
• Hydrogen sulfide (H2S) is a metabolite with dual roles in cellular respiration, acting as both a substrate and an inhibitor.
• High luminal sulfide concentrations are found in the colon due to microbial activity.

Purpose of the Study:

• To investigate the impact of chronic hydrogen sulfide exposure on mitochondrial architecture and function in colon-derived cells.
• To explore the molecular mechanisms underlying sulfide-induced mitochondrial changes.
• To assess the potential role of sulfide as an endogenous regulator of mitochondrial dynamics.

Main Methods:

• Culture of colonocyte-derived cells with chronic exposure to hydrogen sulfide.
• Analysis of mitochondrial morphology, networking, and cristae structure.
• Assessment of inner mitochondrial membrane potential and protein cleavage (Opa1).
• Measurement of electron transport chain complex activities (CI and CIV).

Main Results:

• Chronic sulfide exposure led to reduced expression of Mic60 and Mic19, decreased mitochondrial networking, and loss of cristae.
• Sulfide-induced inner mitochondrial membrane depolarization activated Oma1-dependent Opa1 cleavage.
• Significant loss of activities for respiratory chain complexes CI and CIV was observed.
• Disruption of mitochondrial networks was reversible upon sulfide removal.

Conclusions:

• Hydrogen sulfide acts as an endogenous modulator of mitochondrial dynamics and ultrastructure.
• Sulfide-induced mitochondrial dysfunction involves inner membrane depolarization and respiratory complex impairment.
• Dysregulation of sulfide metabolism may contribute to mitochondrial pathology in certain diseases.