2014 | Katherine R. Parzych and Daniel J. Klionsky
Autophagy is a conserved eukaryotic process that degrades cytoplasmic components, recycling materials for cell survival and maintenance. Dysfunction of autophagy contributes to various human diseases, including neurodegeneration, cancer, and metabolic disorders. This review summarizes current knowledge of mammalian autophagy, focusing on its morphology, molecular mechanisms, regulation, and selectivity.
Autophagy occurs in three forms: microautophagy, macroautophagy, and chaperone-mediated autophagy (CMA). Microautophagy involves direct uptake of cargo into lysosomes via membrane invagination. CMA is highly specific, using chaperones to recognize and transport proteins containing a pentapeptide motif to lysosomes for degradation. Macroautophagy, the best studied, involves the formation of double-membrane autophagosomes that sequester cargo and deliver it to lysosomes for degradation. It plays a critical role in cellular maintenance and survival under stress conditions.
Macroautophagy is regulated by various signaling pathways, including the mTOR pathway, which senses nutrient availability. Under nutrient deprivation, mTOR is inhibited, allowing autophagy to proceed. AMP-activated protein kinase (AMPK) also regulates autophagy by sensing energy levels and modulating mTOR activity. Additionally, ER stress and hypoxia can induce autophagy through different mechanisms.
Selective autophagy targets specific organelles and proteins, such as peroxisomes (pexophagy) and mitochondria (mitophagy). These processes are essential for cellular homeostasis and the clearance of damaged components. The regulation of autophagy involves complex interactions between kinases, phosphatases, and signaling pathways, with ongoing research aimed at understanding these mechanisms.
Despite significant progress, many aspects of autophagy regulation remain unclear. Understanding these mechanisms is crucial for developing therapies targeting autophagy-related diseases. The review highlights the importance of autophagy in human health and the need for further research to elucidate its regulatory networks and functional roles.Autophagy is a conserved eukaryotic process that degrades cytoplasmic components, recycling materials for cell survival and maintenance. Dysfunction of autophagy contributes to various human diseases, including neurodegeneration, cancer, and metabolic disorders. This review summarizes current knowledge of mammalian autophagy, focusing on its morphology, molecular mechanisms, regulation, and selectivity.
Autophagy occurs in three forms: microautophagy, macroautophagy, and chaperone-mediated autophagy (CMA). Microautophagy involves direct uptake of cargo into lysosomes via membrane invagination. CMA is highly specific, using chaperones to recognize and transport proteins containing a pentapeptide motif to lysosomes for degradation. Macroautophagy, the best studied, involves the formation of double-membrane autophagosomes that sequester cargo and deliver it to lysosomes for degradation. It plays a critical role in cellular maintenance and survival under stress conditions.
Macroautophagy is regulated by various signaling pathways, including the mTOR pathway, which senses nutrient availability. Under nutrient deprivation, mTOR is inhibited, allowing autophagy to proceed. AMP-activated protein kinase (AMPK) also regulates autophagy by sensing energy levels and modulating mTOR activity. Additionally, ER stress and hypoxia can induce autophagy through different mechanisms.
Selective autophagy targets specific organelles and proteins, such as peroxisomes (pexophagy) and mitochondria (mitophagy). These processes are essential for cellular homeostasis and the clearance of damaged components. The regulation of autophagy involves complex interactions between kinases, phosphatases, and signaling pathways, with ongoing research aimed at understanding these mechanisms.
Despite significant progress, many aspects of autophagy regulation remain unclear. Understanding these mechanisms is crucial for developing therapies targeting autophagy-related diseases. The review highlights the importance of autophagy in human health and the need for further research to elucidate its regulatory networks and functional roles.