Mechanism and regulation of protein degradation in liver

Mortimore, Glenn E.; Pösö, A.R.; Lardeux, Bernard

doi:10.1002/dmr.5610050105

Cited by 214 publications

(119 citation statements)

References 94 publications

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“…isotopic labeling | protein | turnover | degradation | in vivo P rotein molecules are in dynamic equilibrium in vivo: they are continuously synthesized and degraded during the lifetime of the organism (1,2). The turnover rate of proteins can vary from minutes to years, often conforming to their biological functions (3,4).…”

mentioning

confidence: 99%

Analysis of proteome dynamics in the mouse brain

Price

Guan²,

Burlingame³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

339

447

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Fig. 2. (A)Interaction web of top-down and bottom-up effects in the eelgrass study system. The top predator is the sea otter (E. lutris), the mesopredators are crabs (Cancer spp. and Pugettia producta), the epiphyte mesograzers are primarily an isopod (I. resecata) and a sea slug (P. taylori), and algal epiphyte competitors of eelgrass primarily consist of chain-forming diatoms, and the red alga Smithora naiadum. Solid arrows indicate direct effects, dashed arrows indicate indirect effects, and the plus and minus symbols indicate positive and/or negative effects on trophic guilds and eelgrass condition. C, competitive interaction; T, trophic interaction. (Original artwork by A. C. Hughes.) (B-E) Survey results testing for the effects of sea otter density on eelgrass bed community properties (Tables S2 and S3). Elkhorn Slough (sea otters present and high nutrients) eelgrass beds (n = 4) are coded in red, and the Tomales Bay reference site (no sea otters, low nutrients) beds (n = 4) are coded in blue. (B) Crab biomass and size structure of two species of Cancer crabs; (C) grazer biomass per shoot and large grazer density; (D) algal epiphyte loading; and (E) aboveground and belowground eelgrass biomass. DW, dry weight; FW, fresh weight.

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mentioning

confidence: 99%

Analysis of proteome dynamics in the mouse brain

Price

Guan²,

Burlingame³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

339

447

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“…Lysosomes incorporate proteins for degradation by a variety of pathways such as endocytosis, crinophagy, microautophagy, macroautophagy and direct protein transport ( b o p et al, 1993;Dunn, 1994). Microautophagy (nonselective sequestration of small bits of cytoplasm within lysosomes) appears to be the main lysosomal pathway operating under basal conditions (Mortimore et al, 1989). An enhanced macroautophagy (the nonselective sequestration of a large portion of the cytoplasm), which is regulated by the levels of macroautophagy-suppressing amino acids, is known to increase under conditions of acute starvation (Mortimore et al, 1989;Wing et al, 1991 ;Seglen and Bohley, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…Microautophagy (nonselective sequestration of small bits of cytoplasm within lysosomes) appears to be the main lysosomal pathway operating under basal conditions (Mortimore et al, 1989). An enhanced macroautophagy (the nonselective sequestration of a large portion of the cytoplasm), which is regulated by the levels of macroautophagy-suppressing amino acids, is known to increase under conditions of acute starvation (Mortimore et al, 1989;Wing et al, 1991 ;Seglen and Bohley, 1992). Proteasomes were detected in autophagic vacuoles and, under conditions of starvation, the lysosomal degradation of proteasomes increases.…”

Section: Discussionmentioning

confidence: 99%

“…Katunuma and Kominami, 1985), and (b) that there is an increase in lysosomal proteolysis under conditions of starvation (e.g. Mortimore et al, 1989;Dice, 1990), to investigate the possible role of lysosomes in the degradation of rat liver proteasomes. The results clearly demonstrate the presence of proteasomes in lysosomes prepared from the liver of leupeptintreated or starved rats and are consistent with the participation of the lysosomal pathway in the degradation of proteasomes under fed conditions and starvation by nonselective autophagy, but probably also by the specific transport to lysosomes mediated by a heat-shock cognate protein of 73 kDa (hsc73).…”

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confidence: 99%

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Degradation of Proteasomes by Lysosomes in Rat Liver

Cuervo

Palmer

Rivett

et al. 1995

European Journal of Biochemistry

103

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Proteasomes are high-molecular-mass multisubunit complexes which are believed, either by themselves or as a part of the 26s proteinase complex, to play a central role in extralysosomal pathways of intracellular protein breakdown. We have addressed the degradation of proteasomes in rat liver, investigating the possible role of lysosomes. Affinity-purified antibodies against rat liver proteasomes were used for inimunoblot analysis of isolated lysosomes. Although proteasomes are not found in lysosomes from normally fed rats, they were found to accumulate in lysosomes of rats treated with leupeptin (an inhibitor of lysosomal proteases) and could also be detected in lysosomes isolated from livers of starved (24 h) rats. Proteinase-K treatment of these fractions, as well as immunogold procedures, show that a proportion of the proteasomes are inside lysosomes. Comparison of the amount of proteasomes found in lysosomes by irnmunoblotting with their experimentally determined half life (8.3 days) is consistent with an important role of these organelles in the degradation of rat liver proteasomes. Nevertheless, these data do not exclude the possibility that some nonlysosomal degradation of proteasome components also occurs. Since proteasomes were localized in autophagic vacuoles, it is likely that they are taken up mainly by nonselective autophagy. However, using an in vitro system, it was found that, under conditions of starvation, proteasomes may also be taken up into lysosomes and degraded via the heat-shock cognate protein of 73 MEa (hsc73)-mediated transport.

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“…In addition to nutrients, hormones, most notably insulin and glucagon, are key regulators of autophagy [7,8]; insulin inhibits, whereas glucagon stimulates, autophagy. Autophagy's tight regulation by both nutrient availability and hormones, along with its roles in whole-body metabolism and cellular adaptation to stress, hint at its involvement in the pathophysiology of common metabolic disorders, such as obesity and type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Autophagy in adipose tissue and the beta cell: implications for obesity and diabetes

et al. 2014

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Autophagy is a lysosomal degradation pathway recycling intracellular long-lived proteins and damaged organelles, thereby maintaining cellular homeostasis. In addition to inflammatory processes, autophagy has been implicated in the regulation of adipose tissue and beta cell functions. In obesity and type 2 diabetes autophagic activity is modulated in a tissue-dependent manner. In this review we discuss the regulation of autophagy in adipose tissue and beta cells, exemplifying tissue-specific dysregulation of autophagy and its implications for the pathophysiology of obesity and type 2 diabetes. We will highlight common themes and outstanding gaps in our understanding, which need to be addressed before autophagy could be envisioned as a therapeutic target for the treatment of obesity and diabetes.

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Mechanism and regulation of protein degradation in liver

Cited by 214 publications

References 94 publications

Analysis of proteome dynamics in the mouse brain

Analysis of proteome dynamics in the mouse brain

Degradation of Proteasomes by Lysosomes in Rat Liver

Autophagy in adipose tissue and the beta cell: implications for obesity and diabetes

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