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PreprintCited by 5Cell death mechanisms and regulationAquatic Ecosystems and Phytoplankton DynamicsProtist diversity and phylogeny

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Cathepsin X is a conserved cell death protein involved in algal response to environmental stress

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Mizrachi, Avia, Sadeh, Mai, Ben-Dor, Shifra, Dym, Orly, Ku, Chuan, Feldmesser, Ester, Zarfin, Amichai, Brunson, John K., Allen, Andrew E., Jinkerson, Robert E., Schatz, Daniella, Vardi, Assaf·2024·Current Biology
DOI 10.1101/2024.05.15.594278

Preprint — published as 10.1016/j.cub.2025.03.045 · Paper page

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Abstract

Phytoplankton play a crucial role in global primary production and can form vast blooms in aquatic ecosystems. Bloom demise and the rapid turnover of phytoplankton are suggested to involve programmed cell death (PCD) induced by diverse environmental stressors. However, fundamental knowledge of the PCD molecular components in algae and protists in general remains elusive. Previously, we revealed that early oxidation in the chloroplast predicted subsequent cell death or survival in isogenic subpopulations that emerged following H 2 O 2 treatment in the diatom Phaeodactylum tricornutum . Here, we performed transcriptome analysis of sorted sensitive oxidized cells and resilient reduced cells, to discover genes linked to their contrasting fates. By cross-comparison with a large-scale mutant screen in the green alga Chlamydomonas reinhardtii , we identified functionally relevant conserved PCD gene candidates, including the cysteine protease cathepsin X/Z ( CPX ). CPX mutants in P. tricornutum CPX1 and C. reinhardtii CEP12 both exhibited profound resilience to oxidative stress, supporting a conserved function in algal PCD. P. tricornutum cpx1 mutants, generated using CRISPR-Cas9, also exhibited resilience to the toxic diatom-derived infochemical cyanogen bromide. Phylogenetic and predictive structural analyses show that CPX is highly conserved in eukaryotes, and algae of the green and red lineages exhibit strong structural similarity to human cathepsin CTSZ . CPX is expressed by diverse algae across the oceans and during toxic Pseudo-nitzschia blooms, supporting its ecological importance. Elucidating PCD components in algae sheds light on the evolutionary origin of PCD in unicellular organisms, and on the cellular strategies employed by the population to cope with stressful conditions.

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Metadata

Authors
Mizrachi, A., Sadeh, M., Ben-Dor, S., Dym, O., Ku, C., Feldmesser, E., Zarfin, A., Brunson, J. K., Allen, A. E., Jinkerson, R. E., Schatz, D., & Vardi, A.
Affiliations
  • Weizmann Institute of Science (IL)
  • J. Craig Venter Institute (US)
  • University of California, Riverside (US)
Corresponding author
Vardi, Assaf
ORCID
Venue
Current Biology
Publisher
openRxiv
Published
2024-05-15
Volume
35
Issue
10
Pages
2240-2255.e6
ISSN
0960-9822 (ISSN-L)
DOI
10.1101/2024.05.15.594278
OpenAlex
W4409412786
Cited by
5
References
1
Citations by year
2026: 3 · 2025: 2
FWCI
1.49
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Current Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Israel Science Foundation (749/24, 1972/20)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Physical Sciences › Environmental Science › Environmental Chemistry › Aquatic Ecosystems and Phytoplankton Dynamics
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Protist diversity and phylogeny
Keywords
cathepsin X, programmed cell death, algal cell death, oxidative stress, Phaeodactylum tricornutum, Chlamydomonas reinhardtii, cysteine protease, phytoplankton, cellular heterogeneity, semiochemicals, comparative transcriptomics
MeSH terms
Cathepsins, Phylogeny, Chlamydomonas reinhardtii, Apoptosis, Diatoms, Oxidative Stress, Algal Proteins

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