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Abstract Macroautophagy involves the sequestration of cytoplasmic contents in a double-membrane autophagosome and its subsequent delivery to lysosomes for degradation and recycling. In Caenorhabditis elegans, autophagy participates in diverse processes such as stress resistance, cell fate specification, tissue remodeling, aging, and adaptive immunity. Genetic screens in C. elegans have identified a set of metazoan-specific autophagy genes that form the basis for our molecular understanding of steps unique to the autophagy pathway in multicellular organisms. Suppressor screens have uncovered multiple mechanisms that modulate autophagy activity under physiological conditions. C. elegans also provides a model to investigate how autophagy activity is coordinately controlled at an organismal level. In this chapter, we will discuss the molecular machinery, regulation, and physiological functions of autophagy, and also methods utilized for monitoring autophagy during C. elegans development. 

ABSTRACT The maintenance of a properly folded proteome is critical for cellular function and organismal health, and its age‐dependent collapse is associated with a wide range of diseases. Here, we find that despite the central role of Coenzyme A as a molecular cofactor in hundreds of cellular reactions, inhibition of the first and rate‐limiting step in CoA biosynthesis can be beneficial and promote proteostasis. Impairment of the cytosolic iron–sulfur cluster formation pathway, which depends on Coenzyme A, similarly promotes proteostasis and acts in the same pathway. Proteostasis improvement by interference with the Coenzyme A/iron–sulfur cluster biosynthesis pathways is dependent on the conserved HLH‐30/TFEB transcription factor. Strikingly, under these conditions, HLH‐30 promotes proteostasis by potentiating the expression of select chaperone genes, providing a chaperone‐mediated proteostasis shield, rather than by its established role as an autophagy and lysosome biogenesis‐promoting factor. This reflects the versatile nature of this conserved transcription factor, which can transcriptionally activate a wide range of protein quality control mechanisms, including chaperones and stress response genes alongside autophagy and lysosome biogenesis genes. These results highlight TFEB as a key proteostasis‐promoting transcription factor and underscore it and its upstream regulators as potential therapeutic targets in proteostasis‐related diseases.