Whole genome duplication uncouples cell volume scaling from mitochondrial homeostasis

Polyploidy in Saccharomyces cerevisiae and human diploid-to-tetraploid cells is linked to sub-linear mitochondrial protein scaling, with respiratory chain and redox factors depleted.

• Why it matters: Genome expansion increases cell and nuclear size, but how cells preserve cytonuclear balance and metabolic fitness through mitochondrial homeostasis after polyploidy was unclear.
• What they did: Using isogenic Saccharomyces cerevisiae strains from 1N to 4N and matched human diploid and tetraploid lines, quantitative proteomics assessed mitochondrial protein scaling and composition.
• The result: Impaired mitochondrial scaling is associated with reduced respiratory growth, membrane potential, and oxygen consumption, plus elevated oxidative stress; in yeast, ROS accumulation activates Hog1/cell integrity MAPK and Rtg2-dependent retrograde signaling to promote mitochondrial metabolism despite chronic dysfunction.

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