Mitochondrial aconitase is sensitive to oxidative inactivation and can aggregate and accumulate in many age-related disorders. Here we report that Lon protease, an ATP-stimulated mitochondrial matrix protein, selectively recognizes and degrades the oxidized, hydrophobic form of aconitase after mild oxidative modification, but that severe oxidation results in aconitase aggregation, which makes it a poor substrate for Lon. Similarly, a morpholino oligodeoxynucleotide directed against the lon gene markedly decreases the amount of Lon protein, Lon activity and aconitase degradation in WI-38 VA-13 human lung fibroblasts and causes accumulation of oxidatively modified aconitase. The ATP-stimulated Lon protease may be an essential defence against the stress of life in an oxygen environment. By recognizing minor oxidative changes to protein structure and rapidly degrading the mildly modified protein, Lon protease may prevent extensive oxidation, aggregation and accumulation of aconitase, which could otherwise compromise mitochondrial function and cellular viability. Aconitase is probably only one of many mitochondrial matrix proteins that are preferentially degraded by Lon protease after oxidative modification.

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Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism.

In eukaryotes and prokaryotes, the degradation of most cell proteins requires metabolic energy (Goldberg and St. John, 1976; Hershko and Ciechanover, 1982). This feature of intracellular proteolysis applies not only for cytosolic proteins in bacterial and animal cells. Mitochondria (Desautels and Goldberg, 1982a) and chloroplasts (Malek et al., 1984) also contain systems for complete degradation of abnormal proteins, and this process also requires ATP. An ATP requirement for proteolysis is surprising on thermodynamic grounds, since hydrolysis of peptide bonds should be a spontaneous, exergonic process, and protein breakdown by traditional proteases does not require energy-rich cofactors (Goldberg and St. John, 1976). Initial speculations concerning the energy requirement for proteolysis in eukaryotic cells led to the suggestion that ATP might be necessary for the function of lysosomes in which protein degradation was assumed to occur. However, bacteria lack such organelles, but do show a similar ATP dependence for proteolysis as animal cells (Olden and Goldberg, 1978). Therefore, this requirement must represent a more fundamental property of the degradative process.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1992.tb19822.x

The mechanism and functions of ATP-dependent proteases in bacterial and animal cells.

https://www.jbc.org/content/261/5/2400.full.pdf

Ubiquitin-lysozyme conjugates. Identification and characterization of an ATP-dependent protease from rabbit reticulocyte lysates.

The use of chemicals around the globe in different industries has increased tremendously, affecting the health of people. The modern world intends to replace these noxious chemicals with environmental friendly products for the betterment of life on the planet. Establishing enzymatic processes in spite of chemical processes has been a prime objective of scientists. Various enzymes, specifically microbial proteases, are the most essentially used in different corporate sectors, such as textile, detergent, leather, feed, waste, and others. Proteases with respect to physiological and commercial roles hold a pivotal position. As they are performing synthetic and degradative functions, proteases are found ubiquitously, such as in plants, animals, and microbes. Among different producers of proteases, Bacillus sp. are mostly commercially exploited microbes for proteases. Proteases are successfully considered as an alternative to chemicals and an eco-friendly indicator for nature or the surroundings. The evolutionary relationship among acidic, neutral, and alkaline proteases has been analyzed based on their protein sequences, but there remains a lack of information that regulates the diversity in their specificity. Researchers are looking for microbial proteases as they can tolerate harsh conditions, ways to prevent autoproteolytic activity, stability in optimum pH, and substrate specificity. The current review focuses on the comparison among different proteases and the current problems faced during production and application at the industrial level. Deciphering these issues would enable us to promote microbial proteases economically and commercially around the world.

/pdf/microbial-proteases-applications-o4nt9ikd6n.pdf

T Kimura

Papers

ATP-dependent protease in bovine adrenal cortex. Tissue specificity, subcellular localization, and partial characterization.