Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan

Area of Science:

• Cellular Biology
• Molecular Biology
• Aging Research

Background:

• Chaperones are essential for maintaining protein homeostasis (proteostasis) in cells under optimal conditions.
• Disruptions in protein folding can lead to cellular dysfunction and disease.

Purpose of the Study:

• To investigate the cell-wide consequences of impaired chaperone function in different cellular compartments (cytosol, mitochondria, endoplasmic reticulum) in budding yeast.
• To identify and characterize a potential communication pathway between cellular compartments in response to proteotoxicity.

Main Methods:

• Experimental manipulation of chaperone function in specific cellular compartments of budding yeast.
• Assessment of cellular respiration, proteostasis, and lifespan.
• Analysis of molecular markers associated with cellular stress responses.

Main Results:

• Loss of chaperone activity in any of the studied compartments led to a decline in cellular respiration, indicating a dependence on cell-wide proteostasis.
• Chaperone deficiency induced a coordinated response across cellular compartments, termed the cross-organelle stress response (CORE).
• The CORE pathway involves activation of protein maintenance, antioxidant enzymes, and metabolic adjustments, extending yeast lifespan.

Conclusions:

• Cellular organelles are functionally integrated, communicating through pathways like CORE to maintain proteostasis.
• The CORE pathway acts as a protective mechanism against moderate proteotoxicity and age-related decline.
• Understanding organelle communication is crucial for addressing aging and age-related diseases.