Protein degradation in rat liver during post-natal development

Russell, S M; Burgess, Rowland J.; Mayer, R. John

doi:10.1042/bj1920321

Cited by 37 publications

(22 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While the bulk of mitochondrial proteins are stable for 3.5-5 days in mammalian cells, (5-aminolevinulate synthase has a half-life of only 20 80 min [5,7]. At least two ATP-dependent proteases seem to exist in this mitochondrial compartment; they represent homologues of the ATP-dependent Lon-and Clp-like proteases of prokaryotes.…”

Section: Atp-dependent Proteolysis Of Matrix-localized Proteinsmentioning

confidence: 99%

“…This process is predominant under starvation conditions and results in the nonselective removal of mitochondrial proteins [3]. On the other hand, observed differences in the turnover rates of mitochondrial proteins located in different compartments and of individual proteins in the same compartment have suggested rather early on the existence of proteases within mitochondria [4][5][6]. More recently, a series of proteases have been identified in the mitochondrial matrix space and in the inner membrane which mediate the selective degradation of mitochondrial proteins.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Regulated protein degradation in mitochondria

Langer

Neupert

1996

Experientia

View full text Add to dashboard Cite

Various adenosine triphosphate (ATP)-dependent proteases were identified within mitochondria which mediate selective mitochondrial protein degradation and fulfill crucial functions in mitochondrial biogenesis. The matrix-localized PIM1 protease, a homologue of the Escherichia coli Lon protease, is required for respiration and maintenance of mitochondrial genome integrity. Degradation of non-native polypeptides by PIM1 protease depends on the chaperone activity of the mitochondrial Hsp70 system, posing intriguing questions about the relation between the proteolytic system and the folding machinery in mitochondria. The mitochondrial inner membrane harbors two ATP-dependent metallopeptidases, the m- and the i-AAA protease, which expose their catalytic sites to opposite membrane surfaces and cooperate in the degradation of inner membrane proteins. In addition to its proteolytic activity, the m-AAA protease has chaperone-like activity during the assembly of respiratory and ATP-synthase complexes. It constitutes a quality control system in the inner membrane for membrane-embedded protein complexes.

show abstract

Section: Atp-dependent Proteolysis Of Matrix-localized Proteinsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulated protein degradation in mitochondria

Langer

Neupert

1996

Experientia

View full text Add to dashboard Cite

show abstract

“…However, different mitochondrial proteins turn over at distinct rates. Outer membrane proteins tend to be degraded at a faster rate than those of the inner membrane (6). Furthermore, individual proteins within the same mitochondrial compartment can also have different turnover rates.…”

mentioning

confidence: 99%

“…Furthermore, individual proteins within the same mitochondrial compartment can also have different turnover rates. In the matrix, several enzymes have tl/2 ranging from 70 min to 1-2 days, whereas the bulk of mitochondrial proteins turn over with a tl/2 of 3-5 days (6)(7)(8). Such observations cannot be explained by indiscriminate degradation of this organelle within the lysosome.…”

mentioning

confidence: 99%

Liver mitochondria contain an ATP-dependent, vanadate-sensitive pathway for the degradation of proteins.

Desautels¹,

Goldberg²

1982

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

114

View full text Add to dashboard Cite

A large fraction (30-50%) of the various proteins synthesized within isolated rat liver mitochondria were degraded to amino acids within 60 min after synthesis. Incomplete mitochondrial polypeptides resulting from the incorporation of puromycin were degraded even more extensively (80% per hr). Protein breakdown was measured by the appearance of acid-soluble radioactivity and by the disappearance of labeled polypeptides detected on NaDodSO4/polyacrylamide gel electrophoresis. The amino acids generated by proteolysis were transported rapidly out of the mitochondria and no peptide intermediates accumulated in the organelle. This degradative process did not involve lysosomes or lysosomal enzymes and was markedly stimulated by ATP either generated within the mitochondria or supplied exogenously. An inhibitor of respiration (cyanide) or uncouplers of oxidative phosphorylation (oligomycin, dinitrophenol) reduced proteolysis when mitochondria were provided substrates for ATP generation. When exogenous ATP was provided, these agents did not affect proteolysis, but degradation was then sensitive to atractyloside, an inhibitor of adenine nucleotide transport. Vanadate, an inhibitor of various ATPases, blocked proteolysis even in the presence of ATP and caused a marked stabilization of nearly all polypeptide bands. Thus, mitochondria-like bacteria or the cytosol of animal cells-contain a pathway for complete degradation of proteins which seems to selectively remove polypeptides with abnormal structures. Within this organelle, ATP hydrolysis appears necessary for an initial step in this degradative process.The proteins comprising the mitochondria, like other proteins in mammalian cells, are subject to continual turnover (1). It has generally been assumed that mitochondria are degraded within the lysosome (2-5), and under certain conditions whole mitochondria or mitochondrial enzymes have been demonstrated within autophagic vacuoles (2-4). However, different mitochondrial proteins turn over at distinct rates. Outer membrane proteins tend to be degraded at a faster rate than those of the inner membrane (6). Furthermore, individual proteins within the same mitochondrial compartment can also have different turnover rates. In the matrix, several enzymes have tl/2 ranging from 70 min to 1-2 days, whereas the bulk of mitochondrial proteins turn over with a tl/2 of 3-5 days (6-8). Such observations cannot be explained by indiscriminate degradation of this organelle within the lysosome.One possible explanation for this heterogeneity in degradative rates is that proteins may be excreted by the mitochondria for degradation in the cytoplasm or lysosome. Another possibility is that there exists within mitochondria a proteolytic system that selectively hydrolyzes the short-lived enzymes. Several groups have reported proteases associated with the mitochondrial fraction of mammalian cells (9-14). However, an intramitochondrial localization has not been demonstrated definitively for any of these enzymes. The presence in the mitochon...

show abstract

“…Monoamine oxidase is degraded (Fig. 4a) at a similar rate to that measured in rat liver in vivo (t, 63 h; Tipton & Della Corte, 1979;Russell et al, 1980). The degradation of endogenous [3H]pargyline-labelled monoamine oxidase is dramatically inhibited by methylamine (approx.…”

Section: Resultsmentioning

confidence: 72%

Comparison of the degradative fate of monoamine oxidase in endogenous and transplanted mitochondrial outer membrane in rat hepatocytes. Implications for the cytomorphological basis of protein catabolism

Evans¹,

Mayer²

1984

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

The degradative fate of monoamine oxidase in endogenous and transplanted mitochondrial outer membrane has been compared in rat hepatocyte monolayers. Monoamine oxidase was specifically irreversibly radiolabelled by the suicide inhibitor [3H]pargyline. Hepatocyte monolayers were cultured in conditions in which rates of protein catabolism like those in vivo are maintained [Evans & Mayer (1983) Biochem. J. 216, 151-161]. Incubation of hepatocyte monolayers for 17 h with [3H]pargyline specifically radiolabels mitochondrial monoamine oxidase, as shown by Percoll-gradient fractionation of broken hepatocytes. Monoamine oxidase is degraded at a similar rate to that observed in liver in vivo (t1/2 approx. 63 h). The effects of leupeptin, methylamine and colchicine on the degradation of endogenous radiolabelled enzyme has been studied over prolonged culture periods. Culture of hepatocytes for periods of up to 80 h with inhibitors was not cytotoxic, as demonstrated by measurements of several intrinsic biochemical parameters. Leupeptin, methylamine and colchicine inhibit the degradation of endogenous monoamine oxidase by 60, 38 and 18% respectively. Monoamine oxidase in mitochondrial-outer-membrane vesicles introduced into hepatocytes by poly(ethylene glycol)-mediated vesicle-cell transplantation is degraded at a similar rate (t1/2 55 h) to the endogenous mitochondrial enzyme. Whereas leupeptin inhibits the degradation of endogenous and transplanted enzyme to a similar extent, methylamine and colchicine inhibit the degradation of transplanted enzyme to a much greater extent (85 and 56% respectively). Fluorescence microscopy (with fluorescein isothiocyanate-conjugated mitochondrial outer membrane) shows that transplanted mitochondrial outer membrane undergoes internalization and translocation to a sided perinuclear site, as observed previously with whole mitochondria [Evans & Mayer (1983) Biochem. J. 216, 151-161]. The effects of the inhibitors on the distribution of transplanted membrane material in the cell and inhibition of proteolysis show the importance of cytomorphology for intracellular protein catabolism.

show abstract

Protein degradation in rat liver during post-natal development

Cited by 37 publications

References 46 publications

Regulated protein degradation in mitochondria

Regulated protein degradation in mitochondria

Liver mitochondria contain an ATP-dependent, vanadate-sensitive pathway for the degradation of proteins.

Comparison of the degradative fate of monoamine oxidase in endogenous and transplanted mitochondrial outer membrane in rat hepatocytes. Implications for the cytomorphological basis of protein catabolism

Contact Info

Product

Resources

About