Autophagy and metacaspase determine the mode of cell death in plants

Minina, Elena A.; Filonova, Lada; Fukada, Kazutake; Savenkov, Eugene I.; Gogvadze, Vladimir; Clapham, David; Sánchez-Vera, Victoria; Suárez, María Fernanda; Zhivotovsky, Boris; Daniel, Geoffrey; Smertenko, Andrei; Bozhkov, Peter V.

doi:10.1083/jcb.201307082

Cited by 139 publications

(145 citation statements)

References 56 publications

(87 reference statements)

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“…Their involvement in controlling autophagic flux has been documented in vacuolar PCD (vPCD) during plant development [113], [115], [116] where activity of type IImetacaspase (mcII-Pa) was detected prior to vPCD of embryo-supporting tissue [116]. Metacaspase and autophagy upregulation was measured following the knock-down of either core Atgs or mcII-Pa respectively [115]. It was subsequently reported that mcII-Pa may operate as an upstream positive mediator of autophagic flux, by potentially cleaving or interacting in some other way with an as of yet uncharacterized suppressor of autophagy in plants [115], [116].…”

Section: Functional Conservation Of the Caspase-autophagy Cross-regulmentioning

confidence: 99%

“…Metacaspase and autophagy upregulation was measured following the knock-down of either core Atgs or mcII-Pa respectively [115]. It was subsequently reported that mcII-Pa may operate as an upstream positive mediator of autophagic flux, by potentially cleaving or interacting in some other way with an as of yet uncharacterized suppressor of autophagy in plants [115], [116].…”

Section: Functional Conservation Of the Caspase-autophagy Cross-regulmentioning

confidence: 99%

“…However, despite their functional homology as well as some sequence similarities with caspases, metacaspases also bear striking differences such as cleaving of their substrates after an arginine or lysine residue, instead of aspartate [113], [114]. Their involvement in controlling autophagic flux has been documented in vacuolar PCD (vPCD) during plant development [113], [115], [116] where activity of type IImetacaspase (mcII-Pa) was detected prior to vPCD of embryo-supporting tissue [116]. Metacaspase and autophagy upregulation was measured following the knock-down of either core Atgs or mcII-Pa respectively [115].…”

Section: Functional Conservation Of the Caspase-autophagy Cross-regulmentioning

confidence: 99%

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Caspase involvement in autophagy

2017

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Caspases are a family of cysteine proteases widely known as the principal mediators of the apoptotic cell death response, but considerably less so as the contributors to the regulation of pathways outside cellular demise. In regards to autophagy, the modulatory roles of caspases have only recently begun to be adequately described. In contrast to apoptosis, autophagy promotes cell survival by providing energy and nutrients through the lysosomal degradation of cytoplasmic constituents. Under basal conditions autophagy and apoptosis cross-regulate each other through an elaborate network of interconnections which also includes the interplay between autophagyrelated proteins (ATGs) and caspases. In this review we focus on the effects of this crosstalk at the cellular level, as we aim to concentrate the main observations from research conducted so far on the fine-tuning of autophagy by caspases. Several members of this protease-family have been found to directly interact with key ATGs involved in different tiers across the autophagic cascade. Therefore, we firstly outline the core mechanism of macroautophagy in brief. In an effort to emphasize the importance of the intricate cross-regulation of ATGs and caspases, we also present examples drawn from Drosophila and plant models regarding the contribution of autophagy to apoptotic cell death during normal development. Keywords and abbreviationsautophagy; macroautophagy; mammals; caspases; apoptosis; crosstalk; regulation AMBRA-1Activating-molecule-in-Beclin1-regulated-autophagy-1 AMPK AMP-activated-protein-kinase ATG Autophagy-related gene ATG14L ATG14-likeBcl-2 B-cell lymphoma 2 • Autophagy is implicated in many physiological and pathological processes, where apoptosis is also involved DISC Death-inducing signalling complex FADD Fas-associated protein with death domain Open Questions• Does control of autophagy by caspases represent a central or a supplementary mode of regulation of this pathway?• Is caspase activation required to control autophagy?• To what extent do caspases affect autophagy and how exactly their effects on the pathway vary across different contexts?4

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Section: Functional Conservation Of the Caspase-autophagy Cross-regulmentioning

confidence: 99%

Section: Functional Conservation Of the Caspase-autophagy Cross-regulmentioning

confidence: 99%

Section: Functional Conservation Of the Caspase-autophagy Cross-regulmentioning

confidence: 99%

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Caspase involvement in autophagy

2017

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“…Autophagy has an opposing, pro-death role during developmentally regulated cell death 14,15 or during the pathogentriggered hypersensitive response PCD (hereafter, HR) that occurs locally at the site of attempted pathogen attack.…”

mentioning

confidence: 99%

“…8 Autophagy has an essential, pro-survival role in situations where there is an increasing load of damaged proteins and organelles that need to be eliminated, that is, during aging or stress. Autophagy has an opposing, pro-death role during developmentally regulated cell death 14,15 or during the pathogentriggered hypersensitive response PCD (hereafter, HR) that occurs locally at the site of attempted pathogen attack. 16,17 The dual pro-death/pro-survival functions of plant autophagy remain a topic of active debate.…”

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confidence: 99%

The plant metacaspase AtMC1 in pathogen-triggered programmed cell death and aging: functional linkage with autophagy

et al. 2014

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Autophagy is a major nutrient recycling mechanism in plants. However, its functional connection with programmed cell death (PCD) is a topic of active debate and remains not well understood. Our previous studies established the plant metacaspase AtMC1 as a positive regulator of pathogen-triggered PCD. Here, we explored the linkage between plant autophagy and AtMC1 function in the context of pathogen-triggered PCD and aging. We observed that autophagy acts as a positive regulator of pathogen-triggered PCD in a parallel pathway to AtMC1. In addition, we unveiled an additional, pro-survival homeostatic function of AtMC1 in aging plants that acts in parallel to a similar pro-survival function of autophagy. This novel pro-survival role of AtMC1 may be functionally related to its prodomain-mediated aggregate localization and potential clearance, in agreement with recent findings using the single budding yeast metacaspase YCA1. We propose a unifying model whereby autophagy and AtMC1 are part of parallel pathways, both positively regulating HR cell death in young plants, when these functions are not masked by the cumulative stresses of aging, and negatively regulating senescence in older plants. An emerging theme in cell death research is that cellular processes thought to be regulated by linear signaling pathways are, in fact, complex. Autophagy, initially considered merely a nutrient recycling mechanism necessary for cellular homeostasis, was recently shown to regulate cell death, mechanistically interacting with components that control apoptosis. Deficient autophagy can result in apoptosis [1][2][3] and autophagy hyper-activation can also lead to programmed cell death (PCD). 4 In addition, the pro-survival function of autophagy is mediated by apoptosis inhibition and apoptosis mediates autophagy, although this cross-regulation is not fully understood. 5In plants, autophagy can also have both pro-survival and pro-death functions. Autophagy-deficient plants exhibit accelerated senescence, 6-8 starvation-induced chlorosis, 6,7,9 hypersensitivity to oxidative stress 10 and endoplasmic reticulum stress.11 Further, autophagy-deficient plants cannot limit the spread of cell death after infection with tissue-destructive microbial infections.12,13 The plant phytohormone salicylic acid (SA) mediates most of these phenotypes.8 Autophagy has an essential, pro-survival role in situations where there is an increasing load of damaged proteins and organelles that need to be eliminated, that is, during aging or stress. Autophagy has an opposing, pro-death role during developmentally regulated cell death 14,15 or during the pathogentriggered hypersensitive response PCD (hereafter, HR) that occurs locally at the site of attempted pathogen attack. 16,17The dual pro-death/pro-survival functions of plant autophagy remain a topic of active debate.Also under scrutiny are possible novel functions of caspases and caspase-like proteins as central regulators of pro-survival processes. Caspases were originally defined as executioners of PCD in an...

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Plant type I metacaspases are proteolytically active proteases despite their hydrophobic nature

2021

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Plant metacaspases type I (MCA‐Is), the closest structural homologs of caspases, are key proteases in stress‐induced regulated cell death processes in plants. However, no plant MCA‐Is have been characterized in vitro to date. Here, we show that only plant MCA‐Is contain a highly hydrophobic loop within the C terminus of their p10 domain. When removed, soluble and proteolytically active plant MCA‐Is can be designed and recombinantly produced. We show that the activity of MCA‐I depends on calcium ions and that removal of the hydrophobic loop does not affect cleavage and covalent binding to its inhibitor SERPIN. This novel approach will finally allow the development of tools to detect and manipulate the activity of these cysteine proteases in vivo and in planta.

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Autophagy and metacaspase determine the mode of cell death in plants

Abstract: Metacaspase-dependent autophagy in plants promotes cell disassembly during vacuolar cell death and inhibits necrosis.

Cited by 139 publications

References 56 publications

Caspase involvement in autophagy

Caspase involvement in autophagy

The plant metacaspase AtMC1 in pathogen-triggered programmed cell death and aging: functional linkage with autophagy

Plant type I metacaspases are proteolytically active proteases despite their hydrophobic nature

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