Potassium ion homeostasis modulates mitochondrial function

Area of Science:

• Cell Biology
• Aging Research
• Mitochondrial Biology

Background:

• Age-associated decline in mitochondrial membrane potential (MMP) is linked to aging and related diseases.
• The causal role of MMP decline in aging remains unclear, questioning the viability of interventions targeting MMP.

Purpose of the Study:

• To identify genetic factors influencing age-associated MMP decline using a screening platform.
• To investigate whether modulating MMP can impact lifespan and promote healthier aging.

Main Methods:

• Developed a screening platform in Saccharomyces cerevisiae (yeast) to identify mutations affecting MMP.
• Characterized the longest-lived mutant to understand the mechanisms of MMP maintenance and lifespan extension.
• Tested interventions including gene deletion, enzyme activity modulation, and environmental potassium reduction.

Main Results:

• Identified mutations that slowed or prevented age-associated MMP decline.
• A longest-lived mutant exhibited increased MMP and extended lifespan due to reduced internal potassium.
• Specific interventions, including deleting a potassium transporter and reducing environmental potassium, improved cellular MMP and lifespan.
• In isolated mitochondria, reduced potassium concentration directly increased MMP.

Conclusions:

• Internal potassium levels critically regulate mitochondrial function and cellular lifespan.
• Modulating intracellular potassium is a viable strategy to enhance mitochondrial membrane potential and promote healthier aging.