Proteases in Lens and Cataract

Santhoshkumar, Puttur; Kannan, Rama; Sharma, K. Krishna

doi:10.1007/978-1-4939-1935-2_13

Cited by 3 publications

(2 citation statements)

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“…The degradation of artificially oxidized proteins by AARE enzymes has been demonstrated repeatedly, and silencing of AtAARE in turn increased the levels of oxidized proteins (Fujino et al, 2000; Shimizu et al, 2003; Nakai et al, 2012; Gogliettino et al, 2014). However, a contribution of AARE to the process of aging remained elusive, although several studies associate AARE-function to age-related diseases (Senthilkumar et al, 2001; Santhoshkumar et al, 2015; Palmieri et al, 2017). Additionally, attention is paid to human AARE for potential anti-cancer treatments (Palumbo et al, 2016; Tangri et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

A deeply conserved protease, acylamino acid-releasing enzyme (AARE), acts in ageing in Physcomitrella and Arabidopsis

Hoernstein

Özdemir

Gessel

et al. 2022

Preprint

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Protein oxidation results from the reaction of amino-acid side chains with reactive oxygen species (ROS) and is partly irreversible. In non-photosynthetic tissues, mitochondria are a main source of ROS, whereas plastids are the major source in photosynthetic tissues. Oxidized proteins suffer from decreased structural integrity and even loss of function, and their accumulation leads to cytotoxic aggregates. In mammals, aggregate formation correlates with aging and is linked to several age-related pathologies. Mammalian proteolytic pathways for clearance of oxidized proteins are under intensive research, while mechanistic insights into this process in plants is scarce. Acylamino acid-releasing (AARE) enzymes are ATP-independent serine proteases, presumably acting on oxidized proteins and operating in a dual exo-/endopeptidase mode. They are found in all domains of life. Here, we investigated AARE enzymes in the moss Physcomitrella and the angiosperm Arabidopsis and identified three homologous nuclear genes in Physcomitrella (PpAARE1-3) and a single nuclear gene in Arabidopsis (AtAARE). Surprisingly, we observed triple localization of the proteins AtAARE and PpAARE1 to plastids, mitochondria and the cytosol in vivo, likely conserved across the plant lineage. This represents an ATP-independent possibility for degradation of oxidized proteins in the major source organelles of ROS in plants, which is distinct to mammals. Combinatorial knockout plants and protein interaction analysis revealed specific interactions of the moss AARE isoforms and functions in progressive aging. Analysis of an AtAARE T-DNA mutant further suggests the evolutionary conservation of AARE function in age-related development.

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Section: Discussionmentioning

confidence: 99%

A deeply conserved protease, acylamino acid-releasing enzyme (AARE), acts in ageing in Physcomitrella and Arabidopsis

Hoernstein

Özdemir

Gessel

et al. 2022

Preprint

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“…58 This is not to imply that peptidases are not present in the lens, since like in other tissues, proteolytic activity is required for normal cellular metabolism. For detailed accounts of lens proteolytic enzymes see Santhoshkumar et al 59 and Sharma and Santhoshkumar. 60 It is unlikely that active proteases exist in the center of adult human lenses because, as elaborated above, in the known absence of renewal, this would mean that enzymes Over time, L-Asp and L-Asn residues in lens proteins convert to D-Asp or D-isoAsp.…”

Section: Peptide Bond Cleavagementioning

confidence: 99%

Molecular Processes Implicated in Human Age-Related Nuclear Cataract

Truscott

Friedrich

2019

Invest. Ophthalmol. Vis. Sci.

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Human age-related nuclear cataract is commonly characterized by four biochemical features that involve modifications to the structural proteins that constitute the bulk of the lens: coloration, oxidation, insolubility, and covalent cross-linking. Each of these is progressive and increases as the cataract worsens. Significant progress has been made in understanding the origin of the factors that underpin the loss of lens transparency. Of these four hallmarks of cataract, it is protein-protein cross-linking that has been the most intransigent, and it is only recently, with the advent of proteomic methodology, that mechanisms are being elucidated. A diverse range of cross-linking processes involving several amino acids have been uncovered. Although other hypotheses for the etiology of cataract have been advanced, it is likely that spontaneous decomposition of the structural proteins of the lens, which do not turn over, is responsible for the age-related changes to the properties of the lens and, ultimately, for cataract. Cataract may represent the first and best characterized of a number of human agerelated diseases where spontaneous protein modification leads to ongoing deterioration and, ultimately, a loss of tissue function.

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Role of Proteases in Diabetes and Diabetic Complications

Ravindra

Girish

2017

Proteases in Physiology and Pathology

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Proteases in Lens and Cataract

Cited by 3 publications

References 83 publications

A deeply conserved protease, acylamino acid-releasing enzyme (AARE), acts in ageing in Physcomitrella and Arabidopsis

A deeply conserved protease, acylamino acid-releasing enzyme (AARE), acts in ageing in Physcomitrella and Arabidopsis

Molecular Processes Implicated in Human Age-Related Nuclear Cataract

Role of Proteases in Diabetes and Diabetic Complications

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