Ayyub, C. | Search bioRxiv

bioRxiv2018

Loss of mitochondrial SIRT4 shortens lifespan and leads to a decline in physical activity

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.

physiology↗

bioRxiv2017

Somatic developmental defects in dmrad51/spnA mutant show low temperature sensitivity with enhanced genomic damages and cell death

Homologous Recombination (HR) is one of the key pathways to repair Double Strand Breaks (DSBs). Rad51 serves an important function of catalysing strand exchange between two homologous chromosomes in the HR pathway. In higher organisms, Rad51 function is indispensable with its absence leading to early embryonic lethality, thus precluding any mechanistic probing of the system. In contrast, absence of Drosophila rad51 (Dmrad51/spnA) has been associated with defects in female germline causing ventralization of the egg, without any reported detrimental consequences to Drosophila somatic tissues. In this study, we have performed a systematic analysis of somatic development of dmrad51 null mutant flies by using genetic complementation between multiple dmrad51 alleles. Our current study, for the first time, uncovers the requirement of Dmrad51 in somatic tissue maintenance at both larval and pupal stages. Also, we show that dmrad51 mutant exhibit patterning defects in abdominal cuticle in the stripes and bristles, while there appears to be only subtle defects in the adult wing and eye. Interestingly, dmrad51 null mutant and other alleles show discernible phenotype of low temperature sensitivity, suggesting a role for Dmrad51 in temperature sensitive cellular processes, which thus presents an elegant system for probing temperature sensitive cellular/tissue responses that ensue when a mutation leads to the loss of protein expression (null mutant) rather than its altered protein structure.

developmental biology↗