Nma111p, the pro-apoptotic HtrA-like nuclear serine protease in <i>Saccharomyces cerevisiae</i>: a short survey

Fahrenkrog, Birthe

doi:10.1042/bst0391499

Cited by 11 publications

(5 citation statements)

References 32 publications

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“…Functional analogs, however, remain possible. HtrA proteases related to Ynm3 are present from bacteria to mammals and function in protein quality control, mitochondrial homeostasis, and apoptosis (Clausen et al, 2011;Desideri and Martins, 2012;Fahrenkrog, 2011;Vande Walle et al, 2008). Additionally, human HtrA2 has been implicated in ERAD (Huttunen et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

SHRED Is a Regulatory Cascade that Reprograms Ubr1 Substrate Specificity for Enhanced Protein Quality Control during Stress

et al. 2018

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When faced with proteotoxic stress, cells mount adaptive responses to eliminate aberrant proteins. Adaptive responses increase the expression of protein folding and degradation factors to enhance the cellular quality control machinery. However, it is unclear whether and how this augmented machinery acquires new activities during stress. Here, we uncover a regulatory cascade in budding yeast that consists of the hydrophilin protein Roq1/Yjl144w, the HtrA-type protease Ynm3/Nma111, and the ubiquitin ligase Ubr1. Various stresses stimulate ROQ1 transcription. The Roq1 protein is cleaved by Ynm3. Cleaved Roq1 interacts with Ubr1, transforming its substrate specificity. Altered substrate recognition by Ubr1 accelerates proteasomal degradation of misfolded as well as native proteins at the endoplasmic reticulum membrane and in the cytosol. We term this pathway stress-induced homeostatically regulated protein degradation (SHRED) and propose that it promotes physiological adaptation by reprogramming a key component of the quality control machinery.

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Section: Discussionmentioning

confidence: 99%

SHRED Is a Regulatory Cascade that Reprograms Ubr1 Substrate Specificity for Enhanced Protein Quality Control during Stress

et al. 2018

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“…In contrast, caspase 2 is localized to the nucleus and the Golgi apparatus [54]. The animal apoptotic protease HtrA2/Omi [55] is also released from mitochondria during the apoptotic mitochondrial transition, but the yeast HtrA2 ortholog Nma111p exhibits nuclear localization [56]. Apoptotic DNA-ses EndoG [57] and TNM1 of Tetrahymena are released during apoptosis [58], whereas proteins belonging to the NUC1/apoptotic DNase 2 family have lysosomal localization [59,60].…”

Section: Phylogenetic Analyzesmentioning

confidence: 99%

Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging

2016

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Programmed cell death is a basic cellular mechanism. Apoptotic-like programmed cell death (called apoptosis in animals) occurs in both unicellular and multicellular eukaryotes, and some apoptotic mechanisms are observed in bacteria. Endosymbiosis between mitochondria and eukaryotic cells took place early in the eukaryotic evolution, and some of the apoptotic-like mechanisms of mitochondria that were retained after this event now serve as parts of the eukaryotic apoptotic machinery. Apoptotic mechanisms have several functions in unicellular organisms: they include kin-selected altruistic suicide that controls population size, sharing common goods, and responding to viral infection. Apoptotic factors also have non-apoptotic functions. Apoptosis is involved in the cellular aging of eukaryotes, including humans. In addition, apoptosis is a key part of the innate tumor-suppression mechanism. Several anticancer drugs induce apoptosis, because apoptotic mechanisms are inactivated during oncogenesis. Because of the ancient history of apoptosis, I hypothesize that there is a deep relationship between mitochondrial metabolism, its role in aerobic versus anaerobic respiration, and the connection between apoptosis and cancer. Whereas normal cells rely primarily on oxidative mitochondrial respiration, most cancer cells use anaerobic metabolism. According to the Warburg hypothesis, the remodeling of the metabolism is one of the processes that leads to cancer. Recent studies indicate that anaerobic, non-mitochondrial respiration is particularly active in embryonic cells, stem cells, and aggressive stem-like cancer cells. Mitochondrial respiration is particularly active during the pathological aging of human cells in neurodegenerative diseases. According to the reversed Warburg hypothesis formulated by Demetrius, pathological aging is induced by mitochondrial respiration. Here, I advance the hypothesis that the stimulation of mitochondrial metabolism leads to pathological aging.

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“…An IAP-like protein called BIR1 was identified, and over-expression of BIR1 could both reduce PCD and extend chronological life span (Walter et al, 2006). BIR1 is in turn regulated by a yeast homolog of the mammalian serine protease HtrA2/Omi, called NMA111(Figure 1)(Fahrenkrog, 2011; Fahrenkrog et al, 2004); however, unlike mammalian HtrA2/Omi, which is released from the mitochondria, the yeast NMA111 functions in the nucleus. So far no interaction between BIR1 and YCA1 has been detected (Walter et al, 2006).…”

Section: Pcd In Fungal Agingmentioning

confidence: 99%

Programmed cell death in aging

Tower

2015

Ageing Research Reviews

331

208

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Programmed cell death (PCD) pathways, including apoptosis and regulated necrosis, are required for normal cell turnover and tissue homeostasis. Mis-regulation of PCD is increasingly implicated in aging and aging-related disease. During aging the cell turnover rate declines for several highly-mitotic tissues. Aging-associated disruptions in systemic and inter-cell signaling combined with cell-autonomous damage and mitochondrial malfunction result in increased PCD in some cell types, and decreased PCD in other cell types. Increased PCD during aging is implicated in immune system decline, skeletal muscle wasting (sarcopenia), loss of cells in the heart, and neurodegenerative disease. In contrast, cancer cells and senescent cells are resistant to PCD, enabling them to increase in abundance during aging. PCD pathways limit life span in fungi, but whether PCD pathways normally limit adult metazoan life span is not yet clear. PCD is regulated by a balance of negative and positive factors, including the mitochondria, which are particularly subject to aging-associated malfunction.

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Nma111p, the pro-apoptotic HtrA-like nuclear serine protease in Saccharomyces cerevisiae: a short survey

Cited by 11 publications

References 32 publications

SHRED Is a Regulatory Cascade that Reprograms Ubr1 Substrate Specificity for Enhanced Protein Quality Control during Stress

SHRED Is a Regulatory Cascade that Reprograms Ubr1 Substrate Specificity for Enhanced Protein Quality Control during Stress

Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging

Programmed cell death in aging

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