PT - JOURNAL ARTICLE AU - Sweta Parik AU - Sandipan Tewary AU - Champakali Ayyub AU - Ullas Kolthur-Seetharam TI - Loss of mitochondrial SIRT4 shortens lifespan and leads to a decline in physical activity AID - 10.1101/248831 DP - 2018 Jan 01 TA - bioRxiv PG - 248831 4099 - http://biorxiv.org/content/early/2018/01/16/248831.short 4100 - http://biorxiv.org/content/early/2018/01/16/248831.full AB - Mitochondrial mechanisms and pathways have recently emerged as critical determinants of organismal aging. While nuclear sirtuins have been shown to regulate aging, whether mitochondrial sirtuins do so is still unclear. Here, we report that mitochondrial dSirt4 mediates organismal survival. We establish that absence of dSirt4 leads to reduced lifespan independent of dietary inputs. Further by assaying locomotion, a key correlate of aging, we demonstrate that dSirt4 null flies are severely physically impaired with a significant reduction in locomotion. In summary, we report for the first time that mitochondrial dSirt4 is a key determinant of longevity and its loss leads to early aging.