bims-lypmec 2024-06-02 papers

on Lysosomal positioning and metabolism in cardiomyocytes

Issue of 2024–06–02
two papers selected by
Satoru Kobayashi, New York Institute of Technology

Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status.
Autophagy and machine learning: Unanswered questions.

Sci Rep. 2024 May 31. 14(1): 12521

Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status.

Patricia Marqués, Jesús Burillo, Carlos González-Blanco, Beatriz Jiménez, Gema García, Ana García-Aguilar, Sarai Iglesias-Fortes, Ángela Lockwood, Carlos Guillén.

  Sirtuin1 (SIRT1) activity decreases the tuberous sclerosis complex 2 (TSC2) lysine acetylation status, inhibiting the mechanistic target of rapamycin complex 1 (mTORC1) signalling and concomitantly, activating autophagy. This study analyzes the role of TSC2 acetylation levels in its translocation to the lysosome and the mitochondrial turnover in both mouse embryonic fibroblast (MEF) and in mouse insulinoma cells (MIN6) as a model of pancreatic β cells. Resveratrol (RESV), an activator of SIRT1 activity, promotes TSC2 deacetylation and its translocation to the lysosome, inhibiting mTORC1 activity. An improvement in mitochondrial turnover was also observed in cells treated with RESV, associated with an increase in the fissioned mitochondria, positive autophagic and mitophagic fluxes and an enhancement of mitochondrial biogenesis. This study proves that TSC2 in its deacetylated form is essential for regulating mTORC1 signalling and the maintenance of the mitochondrial quality control, which is involved in the homeostasis of pancreatic beta cells and prevents from several metabolic disorders such as Type 2 Diabetes Mellitus.

Keywords:  Acetylation; Lysosome; Mitophagy; Pancreatic β cells; TSC2; mTORC1

DOI:  https://doi.org/10.1038/s41598-024-63525-7
Biochim Biophys Acta Mol Basis Dis. 2024 May 25. pii: S0925-4439(24)00252-7. [Epub ahead of print]1870(6): 167263

Autophagy and machine learning: Unanswered questions.

Ying Yang, Zhaoying Pan, Jianhui Sun, Joshua Welch, Daniel J Klionsky.

  Autophagy is a critical conserved cellular process in maintaining cellular homeostasis by clearing and recycling damaged organelles and intracellular components in lysosomes and vacuoles. Autophagy plays a vital role in cell survival, bioenergetic homeostasis, organism development, and cell death regulation. Malfunctions in autophagy are associated with various human diseases and health disorders, such as cancers and neurodegenerative diseases. Significant effort has been devoted to autophagy-related research in the context of genes, proteins, diagnosis, etc. In recent years, there has been a surge of studies utilizing state of the art machine learning (ML) tools to analyze and understand the roles of autophagy in various biological processes. We taxonomize ML techniques that are applicable in an autophagy context, comprehensively review existing efforts being taken in this direction, and outline principles to consider in a biomedical context. In recognition of recent groundbreaking advances in the deep-learning community, we discuss new opportunities in interdisciplinary collaborations and seek to engage autophagy and computer science researchers to promote autophagy research with joint efforts.

Keywords:  Artificial intelligence; Lysosome; Macroautophagy; Stress

DOI:  https://doi.org/10.1016/j.bbadis.2024.167263