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Sci Signal. 2017 Feb 28;10(468). pii: eaag2298. doi: 10.1126/scisignal.aag2298.

Target acquired: Selective autophagy in cardiometabolic disease.

Author information

1
Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. brazani@im.wustl.edu.
3
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Abstract

The accumulation of damaged or excess proteins and organelles is a defining feature of metabolic disease in nearly every tissue. Thus, a central challenge in maintaining metabolic homeostasis is the identification, sequestration, and degradation of these cellular components, including protein aggregates, mitochondria, peroxisomes, inflammasomes, and lipid droplets. A primary route through which this challenge is met is selective autophagy, the targeting of specific cellular cargo for autophagic compartmentalization and lysosomal degradation. In addition to its roles in degradation, selective autophagy is emerging as an integral component of inflammatory and metabolic signaling cascades. In this Review, we focus on emerging evidence and key questions about the role of selective autophagy in the cell biology and pathophysiology of metabolic diseases such as obesity, diabetes, atherosclerosis, and steatohepatitis. Essential players in these processes are the selective autophagy receptors, defined broadly as adapter proteins that both recognize cargo and target it to the autophagosome. Additional domains within these receptors may allow integration of information about autophagic flux with critical regulators of cellular metabolism and inflammation. Details regarding the precise receptors involved, such as p62 and NBR1, and their predominant interacting partners are just beginning to be defined. Overall, we anticipate that the continued study of selective autophagy will prove to be informative in understanding the pathogenesis of metabolic diseases and to provide previously unrecognized therapeutic targets.

PMID:
28246200
PMCID:
PMC5451512
DOI:
10.1126/scisignal.aag2298
[Indexed for MEDLINE]
Free PMC Article

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