• ULLAS KOLTHUR-SEETHARAM

      Articles written in Journal of Biosciences

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

      SWETA PARIK SANDIPAN TEWARY CHAMPAKALI AYYUB ULLAS KOLTHUR-SEETHARAM

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      Mitochondrial mechanisms and pathways have recently emerged as critical determinants of organismal aging. Whilenuclear sirtuins have been shown to regulate aging, whether mitochondrial sirtuins do so is still unclear. Here, we report thatmitochondrial dSirt4 mediates organismal aging. We establish that absence of dSirt4 leads to reduced lifespan independentof dietary inputs. Further by assaying locomotion, a key correlate of aging, we demonstrate that dSirt4 null flies are severelyphysically impaired with a significant reduction in locomotion. In summary, we report that mitochondrial dSirt4 is a keydeterminant of longevity and its loss leads to early aging.

    • Metabolic choreography of gene expression: nutrient transactions with the epigenome

      BABUKRISHNA MANIYADATH U S SANDRA ULLAS KOLTHUR-SEETHARAM

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      Eukaryotic complexity and thus their ability to respond to diverse cues are largely driven by varyingexpression of gene products, qualitatively and quantitatively. Protein adducts in the form of post-translationalmodifications, most of which are derived from metabolic intermediates, allow fine tuning of gene expressionat multiple levels. With the advent of high-throughput and high-resolution mapping technologies there hasbeen an explosion in terms of the kind of modifications on chromatin and other factors that govern geneexpression. Moreover, even the classical notion of acetylation and methylation dependent regulation oftranscription is now known to be intrinsically coupled to biochemical pathways, which were otherwiseregarded as ‘mundane’. Here we have not only reviewed some of the recent literature but also havehighlighted the dependence of gene regulatory mechanisms on metabolic inputs, both direct and indirect. Wehave also tried to bring forth some of the open questions, and how our understanding of gene expression haschanged dramatically over the last few years, which has largely become metabolism centric. Finally,metabolic regulation of epigenome and gene expression has gained much traction due to the increasedincidence of lifestyle and age-related diseases.

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