Proteolytic enzymes of rat liver mitochondria. Evidence for a mast cell origin

Haas, R.; Heinrich, Peter C.; Sasse, D.

doi:10.1016/0014-5793(79)81274-0

Cited by 37 publications

(11 citation statements)

References 19 publications

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“…The incorporation, which was not seen in untreated mice, was also accompanied by increased transglutaminase activity (Ginsburg et al, 1963). Since mast cells, including those in liver (Haas et al, 1979), have proteolytic enzymes (Lagunoff and Benditt, 1963;Ende et al, 1964;see Mundy and Strittmatter, 1985;Wintroub et al, 1986), a peptide or peptides containing 7-glutamylhistamine might be released under special circumstances. Other peptides of histamine may exist.…”

Section: Metabolism Of Histaminementioning

confidence: 91%

Aspects of histamine metabolism

et al. 1987

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Section: Metabolism Of Histaminementioning

confidence: 91%

Aspects of histamine metabolism

et al. 1987

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“…To label mitochondrial proteins, isolated mitochondria at a final concentration of 2-3 mg of protein per ml were incubated with [3S]methionine or [3H]leucine at 30°C in sterile buffer 1(90 mM KCV50 mM Hepes/1 mM EDTA/5 mM KH2POJ10 mM MgCl2/0.36 mM cycloheximide) supplemented with 3mM ATP, 5mM phosphoenolpyruvate, pyruvate kinase at 10 ,ug/ml, a mixture ofall amino acids (100 ,uM) except methionine or leucine, [35S]methionine at 12.5 ,uCi/ml (600 Ci/ mmol; 1 Ci = 3.7 x 1010 becquerels; New England Nuclear), and [4,5-3H]leucine at 50 ,uCi/ml (58 Ci/mmol; Schwarz/ Mann) at pH 7.4 (34). After incubation for 20 min with shaking, 15 mM unlabeled methionine or leucine was added to the mixture. The labeled mitochondria were incubated for an additional 5 min, centrifuged, and washed twice with ice-cold 0.25 M sucrose containing 20 mM Hepes (pH 7.4) and 1.0 mM EDTA.…”

Section: Methodsmentioning

confidence: 99%

“…To measure protein breakdown, the labeled mitochondria were resuspended in buffer I plus 15 mM methionine or leucine; they were then incubated at 30°C for 40-60 min. Reactions were terminated by the addition of 10% trichloroacetic acid and of unlabeled mitochondria (3-10 mg) as carrier.…”

Section: Methodsmentioning

confidence: 99%

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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

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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...

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“…However, it has been difficult to exclude the contamination of mitochondrial preparations with proteases from lysosomes or mast cell granules (see, for instance, Rubio and Grisolia 1977;Duque-Magalhães 1979;Haas et al 1979). A major breakthrough was the demonstration of an ATP-dependent protease with a similarity to E. coli Lon (or La) in the matrix of mitochondria from rat liver (Desautels andGoldberg 1982a, 1985), counterparts of which were later found in bovine adrenal cortex (Watabe and Kimura 1985a,b) and yeast (Kutejová et al 1993).…”

Section: Mitochondrial Proteasesmentioning

confidence: 99%