Metabolism catabolism and anabolism1/6/2024 ![]() ![]() MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. A gene network regulating lysosomal biogenesis and function. The lysosome at the intersection of cellular growth and destruction. ![]() Lysosomes as dynamic regulators of cell and organismal homeostasis. A deeper comprehension of lysosomal composition and function, at both the cellular and organismal level, may uncover fundamental insights into human physiology and disease.īallabio, A. Lastly, we discuss how lysosome dysfunction contributes to diverse disease pathologies and how inherited mutations that compromise lysosomal hydrolysis, transport or signalling components lead to multi-organ disorders with severe metabolic and neurological impact. We also highlight the emerging interactions of lysosomes with other organelles, which contribute to cellular homeostasis. In this Review, we discuss recent findings on lysosome-dependent signalling pathways, focusing on how the lysosome senses nutrient availability through its physical and functional association with mechanistic target of rapamycin complex 1 (mTORC1) and how, in response, the microphthalmia/transcription factor E (MiT/TFE) transcription factors exert feedback regulation on lysosome biogenesis. The lysosome orchestrates these key functions through the synchronised interplay between hydrolytic enzymes, nutrient transporters and signalling factors, which together enable metabolic coordination with other organelles and regulation of specific gene expression programmes. ![]() Every cell must satisfy basic requirements for nutrient sensing, utilization and recycling through macromolecular breakdown to coordinate programmes for growth, repair and stress adaptation. ![]()
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