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Cited 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·2025·Current Biology
DOI 10.1016/j.cub.2025.03.045

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Abstract

Phytoplankton are responsible for half of the global photosynthesis and form vast blooms in aquatic ecosystems. Bloom demise fuels marine microbial life and is suggested to be mediated by programmed cell death (PCD) induced by diverse environmental stressors. Despite its importance, the molecular basis for algal PCD remains elusive. Here, we reveal novel PCD genes conserved across distant algal lineages using cell-to-cell heterogeneity in the response of the diatom Phaeodactylum tricornutum to oxidative stress. Comparative transcriptomics of sorted sensitive and resilient subpopulations following oxidative stress revealed genes directly linked to their contrasting fates of cell death and survival. Comparing these genes with those found in a large-scale mutant screen in the green alga Chlamydomonas reinhardtii identified functionally relevant conserved PCD gene candidates, including the cysteine protease cathepsin X/Z (CPX). CPX mutants in P. tricornutum CPX1 and C. reinhardtii CYSTEINE ENDOPEPTIDASE 12 (CEP12) exhibited resilience to oxidative stress and infochemicals that induce PCD, supporting a conserved function of these genes in algal PCD. Phylogenetic and predictive structural analyses show that CPX is highly conserved in eukaryotes, and algae exhibit strong structural similarity to human Cathepsin X/Z (CTSZ), a protein linked to various diseases. CPX is expressed by diverse algae across the oceans and correlates with upcoming demise events during toxic Pseudo-nitzschia blooms, providing support for its ecological significance. 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
Elsevier BV
Published
2025-05
Volume
35
Issue
10
Pages
2240-2255.e6
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2025.03.045
OpenAlex
W4409412786
Cited by
5
References
142
Citations by year
2026: 3 · 2025: 2
FWCI
1.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Israel Science Foundation (1972/20, 749/24)
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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