Loss of DNA Repair Methyltransferase Gene MGT1 Alters Mitochondrial Dynamics and Accelerates Aging in Saccharomyces cerevisiae

The MGT1 gene encodes O⁶-methylguanine-DNA methyltransferase, a highly conserved enzyme that directly reverses alkylation damage by transferring methyl groups from guanine to a catalytic cysteine. While its nuclear function in genome maintenance is well characterized, its contribution to mitochondrial homeostasis remains elusive. Here, we investigated the Δmgt1 mutant of Saccharomyces cerevisiae. Remarkably, the mutant displayed higher colony formation on non-fermentable carbon sources, indicating altered respiratory efficiency. DAPI-based imaging revealed increased and dispersed mitochondrial DNA (mtDNA), with quantitative analysis confirming elevated mtDNA content. Despite this, Δmgt1 cells exhibited a markedly shortened chronological lifespan, suggesting a link between MGT1 deficiency and genomic instability, mitochondrial dysregulation, and accelerated cellular aging. Bioinformatic analyses highlighted interactions with key DNA repair proteins, including Msh6p, Mlh1p, Mre11p, Exo1p, and Ogg1p, suggesting integration into broader genome-stability networks. These findings reveal a previously unrecognized mitochondrial dimension of MGT1 function and raise the intriguing possibility that the plant homolog AtAGT1 may similarly modulate mitochondrial integrity, stress resilience, and lifespan in higher eukaryotes. Plant Tissue Cult. & Biotech. 35(2): 309-320, 2025 (December)