The tale of caspase homologues and their evolutionary outlook: deciphering programmed cell death in cyanobacteria

Abstract

Programmed cell death (PCD), a genetically orchestrated mechanism of cellular demise, is paradoxically required to support life. As in lower eukaryotes and bacteria, PCD in cyanobacteria is poorly appreciated, despite recent biochemical and molecular evidence that supports its existence. Cyanobacterial PCD is an altruistic reaction to stressful conditions that significantly enhances genetic diversity and inclusive fitness of the population. Recent bioinformatic analysis has revealed an abundance of death-related proteases, i.e. orthocaspases (OCAs) and their mutated variants, in cyanobacteria, with the larger genomes of morphologically complex strains harbouring most of them. Sequence analysis has depicted crucial accessory domains along with the proteolytic p20-like sub-domain in OCAs, predicting their functional versatility. However, the cascades involved in sensing death signals, their transduction, and the downstream expression and activation of OCAs remain to be elucidated. Here, we provide a comprehensive description of the attempts to identify mechanisms of PCD and the existence and importance of OCAs based on in silico approaches. We also review the evolutionary and ecological significance of PCD in cyanobacteria. In the future, the analysis of cyanobacterial PCD will identify novel proteins that have varied functional roles in signalling cascades and also help in understanding the incipient mechanism of PCD morphotype(s) from where eukaryotic PCD might have originated.

Cell Death in Cyanobacteria: Current Understanding and Recommendations for a Consensus on Its Nomenclature

“…PCD has been described as part of normal plant development, as well as a response to biotic and abiotic stresses ( Jones, 2001 ; Huysmans et al, 2017 ). Despite research on the subroutines operating in plants has grown considerably in the past few years, their classification, and homology to animal system are still under debate ( van Doorn et al, 2011 ; Huysmans et al, 2017 ; Bhattacharjee and Mishra, 2020 ).…”

“…Nevertheless, the term PCD is the most widely used term to refer to all instances of RCD, and is often used interchangeably with apoptosis ( Franklin et al, 2006 ; Bidle, 2015 ; Hu and Rzymski, 2019 ; Bhattacharjee and Mishra, 2020 ). Notably, the same morphological and biochemical features, in particular cytoplasmic vacuolation, DNA fragmentation, and caspase activity, are claimed to be hallmarks of PCD in some studies ( He et al, 2016 ) while hallmarks of apoptosis in others ( Ding et al, 2012 ; Li et al, 2020 ; Zhou et al, 2020 ).…”

Insights Into the Phylogenetic Distribution, Diversity, Structural Attributes, and Substrate Specificity of Putative Cyanobacterial Orthocaspases

“…Furthermore, the presence of TM infers membrane localization of some OCAs, while others devoid of TM are probably cytosolic. The presence of putative cytosolic and membrane-bound true OCAs depicted the possibility of both intrinsic and extrinsic PCD in cyanobacteria (Bhattacharjee and Mishra, 2020), yet they are poorly appreciated in prokaryotes and require extensive research to validate.…”

“…Energy components Energy ± σ (kcal mol −1 ) HC (a) RR (b) HC-RR (X) Difference (X-a-b) same strain in different clades may also indicate multiple HGT events (Bhattacharjee and Mishra, 2020). Interestingly, the YN pseudo-variant was only harbored by nitrogenfixing multicellular cyanobacteria, whereas the YS variant…”

The Role of Pseudo-Orthocaspase (SyOC) of Synechocystis sp. PCC 6803 in Attenuating the Effect of Oxidative Stress

“…Cyanobacterial orthocaspases were believed to prefer caspase substrates ( Berman-Frank et al, 2004 ; Bar-Zeev et al, 2013 ), however, in vitro prokaryotic orthocaspases do not recognize substrates with aspartic acid (D) residue at the P1 position, but instead prefer positively charged R or K residues ( Klemencic et al, 2015 ; Spungin et al, 2019 ). Interestingly, many bacterial orthocaspases contain substitutions in the HC catalytic site; instead of the catalytic dyad, they display a highly variable pair of residues (Y-S, Y-N, Y-C, H-G,-C-Y, Y-R, Y-G, Y-Y, Y-H, Y-Q, or H-P), which presumably renders them proteolytically inactive ( Klemencic et al, 2019 ; Bhattacharjee and Mishra, 2020 ). Analyzing cyanobacterial genomes, it was observed that all cyanobacteria containing orthocaspases contain a proteolytically inactive variant.…”