Biology subjects

Sumi, T. S.

Publications and source records attributed to Sumi, T. S..

3 recordsLinked to original sources

bioRxiv2025

PARP1 deficiency induces aging-associated cardiac failure via activation of Akt signalling

PARP1, a poly-ADP-ribose transferase, plays a critical role in maintaining genomic stability, transcription, cellular metabolism, and cell death. PARP1 inhibition protects cardiomyocytes against oxidative and genotoxic stress. However, the role of PARP1 in aging-associated heart failure remains poorly explored. In the current study, we report that PARP1 levels are downregulated in aging mouse hearts, and PARP1 deficiency induces aging-related cardiac remodelling and contractile dysfunction in mice. PARP1 deficient mice hearts exhibit spontaneous activation of the Akt signalling pathway, leading to the development of aging-related cardiac hypertrophy and fibrosis. Our findings reveal two distinct mechanisms by which PARP1 regulates Akt signalling, direct interaction of PARP1 with Akt and the transcriptional regulation of phosphatases like PTEN, a negative regulator of Akt signalling. PARP1 binds and inhibits Akt by poly-ADP-ribosylation at E40 and E49 residues, which impairs Akt membrane recruitment and subsequent activation. Inhibition of Akt reversed hypertrophy in PARP1-depleted cardiomyocytes and improved the contractile dysfunction in PARP1-deficient hearts. These findings reveal a previously unrecognized regulatory role for PARP1 in aging-associated cardiac failure.

physiology↗

bioRxiv2025

Sirtuin 2 controls global protein synthesis by regulating Rheb-GTPase

Upregulated global protein synthesis is associated with the development and progression of several diseases and disorders. Strategies like calorie restriction and pharmacological inhibition of protein synthesis, have exhibited health-promoting effects. However, the complex molecular events that regulate global protein synthesis are not completely understood. Here, we report that SIRT2, a histone deacylase, negatively regulates global protein synthesis by inhibiting the mTORC1 pathway via deacetylating Rheb and promoting Rheb degradation. Our in vitro results suggest that SIRT2 deficiency increases protein synthesis, whereas SIRT2 overexpression suppresses protein synthesis. SIRT2-deficient mice exhibit age-associated and neurohormone-induced cardiac hypertrophy. Here, we report increased global protein synthesis in the hearts of young SIRT2-deficient mice, which may contribute to the development of cardiac hypertrophy. Conversely, cardiac-specific overexpression of SIRT2 reduces global protein synthesis in mice hearts. Mechanistically, SIRT2 binds to and deacetylates Rheb at K151 residue to enhance ubiquitin-proteosome-mediated degradation of Rheb. Depletion of Rheb rescues the increased protein synthesis in SIRT2-inhibited conditions. Our findings suggest that SIRT2 activation can be a potential therapeutic for treating diseases associated with increased protein synthesis.

cell biology↗

bioRxiv2023

Mass lysis of bacterial predators drives the enrichment of antibiotic resistance in soil microbial communities

While studies on anthropogenic activities and antibiotic resistance are numerous, the impact of microbial interactions on resistance in complex communities remains uncertain. Here we demonstrate a correlation between the presence of Myxococcus xanthus in natural soil communities and the abundance of antibiotic-resistant bacteria. Further, introducing M. xanthus isolates also enriches antibiotic resistance. This is due to the mass lysis of M. xanthus cells, which results in a toxic environment that fosters the proliferation of pre-existing resistant bacteria rather than de novo resistance evolution. Metagenomic analysis revealed that this enrichment is not limited to the tested antibiotics in culture-based methods, indicating its broader relevance. Crucially, these findings go beyond laboratory settings, showing M. xanthus introduction enriches resistant isolates in natural soil communities. Finally, we demonstrate that the mass lysis of M. xanthus cells during starvation-induced development--key aspect of the lifecycle of M. xanthus--also results in the enrichment of antibiotic resistance in soil communities. Together, we demonstrate how life-history traits in bacterial predators, like M. xanthus, significantly impact antibiotic resistomes in nature. This study also highlights the complex dynamics at play in the evolution and maintenance of antibiotic resistance, emphasizing the role of interspecies interactions in shaping antibiotic resistance profiles.

evolutionary biology↗