Participation of Lysosomes in Cellular Autophagy Induced in Rat Liver by Glucagon

Deter, Russell L.; Baudhuin, Pierre; Duve, Christian de

doi:10.1083/jcb.35.2.c11

Cited by 303 publications

(200 citation statements)

References 5 publications

Supporting

Mentioning

196

Contrasting

Order By: Relevance

“…Autophagy was named morphologically by the observations from electron microscopy of rat hepatic cell lysosomes, where single membrane vesicles, containing cytoplasm or organelles such as mitochondria and endoplasmic reticulum (ER) were observed [12][13][14][15]. Based on Thomas Ashford's and Keith Porter's early findings in 1962 that revealed the presence of sequestered organelles in rat hepatocytes following their exposure to glucagon [12], de Duve and his colleagues confirmed that this hormone can induce autophagy [16]. Subsequently, other researchers further examined the hormonal and enzymatic regulation of autophagy.…”

Section: The History Of Discoverymentioning

confidence: 98%

The machinery of macroautophagy

et al. 2013

View full text Add to dashboard Cite

Autophagy is a primarily degradative pathway that takes place in all eukaryotic cells. It is used for recycling cytoplasm to generate macromolecular building blocks and energy under stress conditions, to remove superfluous and damaged organelles to adapt to changing nutrient conditions and to maintain cellular homeostasis. In addition, autophagy plays a critical role in cytoprotection by preventing the accumulation of toxic proteins and through its action in various aspects of immunity including the elimination of invasive microbes and its participation in antigen presentation. The most prevalent form of autophagy is macroautophagy, and during this process, the cell forms a double-membrane sequestering compartment termed the phagophore, which matures into an autophagosome. Following delivery to the vacuole or lysosome, the cargo is degraded and the resulting macromolecules are released back into the cytosol for reuse. The past two decades have resulted in a tremendous increase with regard to the molecular studies of autophagy being carried out in yeast and other eukaryotes. Part of the surge in interest in this topic is due to the connection of autophagy with a wide range of human pathophysiologies including cancer, myopathies, diabetes and neurodegenerative disease. However, there are still many aspects of autophagy that remain unclear, including the process of phagophore formation, the regulatory mechanisms that control its induction and the function of most of the autophagy-related proteins. In this review, we focus on macroautophagy, briefly describing the discovery of this process in mammalian cells, discussing the current views concerning the donor membrane that forms the phagophore, and characterizing the autophagy machinery including the available structural information.

show abstract

Section: The History Of Discoverymentioning

confidence: 98%

The machinery of macroautophagy

et al. 2013

View full text Add to dashboard Cite

show abstract

“…7 Much of the pioneering work in the autophagy field is conducted in the liver or using isolated hepatocytes, such as determination of the morphology and membrane compositions of autophagosomes and characterization of the kinetics of protein degradation, regulation by hormones and amino acids, and involvement of the mammalian target of rapamycin (mTOR) pathway in induction. 2,[8][9][10][11][12] It is now clear that macroautophagy is important for many physiological and pathological processes. 4,6,13 It is required for normal development and participates in the clearance of apoptotic cells during embryogenesis.…”

Section: The Basics Of Macroautophagymentioning

confidence: 99%

“…8 Soon it was confirmed that glucagon can stimulate autophagy in the liver. 9,25 The glucagon receptor is Gprotein-coupled. The effector of the coupled G␣s is adenylyl cyclase.…”

Section: Role Of Autophagy In Nutrient and Energy Metabolism In Hepatmentioning

confidence: 99%

Autophagy in the liver

2008

View full text Add to dashboard Cite

A great part of our current understanding of mammalian macroautophagy is derived from studies of the liver. The term "autophagy" was introduced by Christian de Duve in part based on ultrastructural changes in rat liver following glucagon injection. Subsequent morphological, biochemical, and kinetics studies of autophagy in the liver defined the basic process of autophagosome formation, maturation, and degradation and the regulation of autophagy by hormones, phosphoinositide 3-kinases, and mammalian target of rapamycin. It is now clear that macroautophagy in the liver is important for the balance of energy and nutrients for basic cell functions, the removal of misfolded proteins resulting from genetic mutations or pathophysiological stimulations, and the turnover of major subcellular organelles such as mitochondria, endoplasmic reticulum, and peroxisomes under both normal and pathophysiological conditions. Disturbance of autophagy function in the liver could thus have a major impact on liver physiology and liver disease. (HEPATOLOGY 2008;47: 1773-1785.)

show abstract

“…The first morphological description of autophagy in mammalian cells was reported in the 1950s. [12][13][14] However, a more detailed understanding of autophagy was accelerated in the 1990s after the identification of autophagy-related (ATG) genes in the yeast S. cerevisiae. 15 Since then, several related ATGs have been identified and are highly conserved in various species.…”

Section: The Process and Regulation Of Autophagymentioning

confidence: 99%