Speaker: Andrey Parkhitko, University of Pittsburgh assistant professor of medicine (endocrinology and metabolism)

Title: "Arginine-specific methylation mediates some of the beneficial effects of methionine restriction"

Abstract: Methionine metabolism is a central regulator of protein synthesis, mitochondrial function, antioxidant defense, and other critical cellular processes. Tight regulation of methionine flux through the methionine metabolism pathway is essential for healthy cellular function. Restricting methionine in the diet (in the absence of cysteine) provides multiple benefits, including protection of rodents against diet-induced obesity and increased lifespan. Accordingly, human population studies demonstrate positive associations between methionine intake and type 2 diabetes, acute coronary events, and mild cognitive impairment. However, we still lack information on the validated downstream effectors that mediate the beneficial effects of methionine restriction (MetR). Methionine and ATP are the sole precursors for the production of S-adenosylmethionine (SAM), the principal and rate-limiting methyl donor for all methyltransferases, which catalyze a variety of methylation reactions by transferring methyl groups to different substrates. To explore which methyltransferases may mediate the beneficial effects of MetR, we used Drosophila to screen most methyltransferases to identify ones that phenocopy MetR in protecting flies against stress. We identified several arginine-specific methyltransferases, including csul/PRMT5, that promote resistance to stress, and this phenotype was conserved in yeast and human cells. We further demonstrated that levels of arginine-specific methylation change with age and under methionine restriction, and that inhibition of these changes extends lifespan and promotes healthspan. 

Host: Ping Kang, GDCB adjunct assistant professor