Loss of PPR protein Ppr2 induces ferroptosis-like cell death in Schizosaccharomyces pombe.
Cell death
Ferroptosis-like cell death
Mitochondria
Pentatricopeptide repeat gene
Δppr2
Journal
Archives of microbiology
ISSN: 1432-072X
Titre abrégé: Arch Microbiol
Pays: Germany
ID NLM: 0410427
Informations de publication
Date de publication:
03 Jun 2022
03 Jun 2022
Historique:
received:
07
03
2022
accepted:
09
05
2022
revised:
30
04
2022
entrez:
3
6
2022
pubmed:
4
6
2022
medline:
9
6
2022
Statut:
epublish
Résumé
Ferroptosis is a form of iron- and lipid peroxidation-mediated programmed cell death that occurs widely in mammalian cells. However, this phenomenon is rarely reported in unicellular eukaryotes. Here, we address whether ferroptosis occurs in the model unicellular eukaryote Schizosaccharomyces pombe (S. pombe). Deletion of the pentatricopeptide repeat (PPR) gene ppr2 encoding as a general mitochondrial translation factor required for mitochondrial translation disrupts iron homeostasis and induces oxidative stress, resulting in loss of cell viability. The small-molecular ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (Fer-1) partially rescued the ppr2 deletion-induced cell death. The amount of malondialdehyde, a lipid peroxidation marker, in Δppr2 cells was higher than that in wild type. Using C11-BODIPY 581/591, an oxidation-sensitive fluorescent lipid peroxidation probe, we showed that Δppr2 cells have a large amount of lipid peroxidation compared to wild-type cells. Deletion of ferric reductase transmembrane component 1 (frp1) encoding S. pombe ferric reductase, which is required for ferric iron uptake, partially rescued the cell death of Δppr2 cells. Our results suggest that ppr2 deletion causes an imbalance in iron homeostasis and redox, leading to ferroptosis-like cell death in S. pombe.
Identifiants
pubmed: 35657410
doi: 10.1007/s00203-022-02970-2
pii: 10.1007/s00203-022-02970-2
doi:
Substances chimiques
Iron
E1UOL152H7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
360Subventions
Organisme : National Natural Science Foundation of China
ID : 31770810
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Ahmad F, Luo Y, Yin H, Zhang Y, Huang Y (2022) Identification and analysis of iron transporters from the fission yeast Schizosaccharomyces pombe. Arch Microbiol 204:152. https://doi.org/10.1007/s00203-021-02683-y
doi: 10.1007/s00203-021-02683-y
pubmed: 35079912
Amorim JA, Coppotelli G, Rolo AP, Palmeira CM, Ross JM, Sinclair DA (2022) Mitochondrial and metabolic dysfunction in ageing and age-related diseases. Nat Rev Endocrinol 18:243–258. https://doi.org/10.1038/s41574-021-00626-7
doi: 10.1038/s41574-021-00626-7
pubmed: 35145250
pmcid: 9059418
Bahler J, Wu JQ, Longtine MS, Shah NG, McKenzie A 3rd, Steever AB, Wach A, Philippsen P, Pringle JR (1998) Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe. Yeast 14:943–951. https://doi.org/10.1002/(SICI)1097-0061(199807)14:10%3c943::AID-YEA292%3e3.0.CO;2-Y
doi: 10.1002/(SICI)1097-0061(199807)14:10<943::AID-YEA292>3.0.CO;2-Y
pubmed: 9717240
Bloemberg D, Quadrilatero J (2019) Autophagy, apoptosis, and mitochondria: molecular integration and physiological relevance in skeletal muscle. Am J Physiol Cell Physiol 317:C111–C130. https://doi.org/10.1152/ajpcell.00261.2018
doi: 10.1152/ajpcell.00261.2018
pubmed: 31017800
pmcid: 6689753
Bock FJ, Tait SWG (2020) Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol 21:85–100. https://doi.org/10.1038/s41580-019-0173-8
doi: 10.1038/s41580-019-0173-8
pubmed: 31636403
Bogacz M, Krauth-Siegel RL (2018) Tryparedoxin peroxidase-deficiency commits trypanosomes to ferroptosis-type cell death. Elife. https://doi.org/10.7554/eLife.37503
doi: 10.7554/eLife.37503
pubmed: 30047863
pmcid: 6117152
Dachert J, Ehrenfeld V, Habermann K, Dolgikh N, Fulda S (2020) Targeting ferroptosis in rhabdomyosarcoma cells. Int J Cancer 146:510–520. https://doi.org/10.1002/ijc.32496
doi: 10.1002/ijc.32496
pubmed: 31173656
Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B III, Stockwell BR (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:1060–1072. https://doi.org/10.1016/j.cell.2012.03.042
doi: 10.1016/j.cell.2012.03.042
pubmed: 22632970
pmcid: 3367386
Forsburg SL, Rhind N (2006) Basic methods for fission yeast. Yeast 23:173–183. https://doi.org/10.1002/yea.1347
doi: 10.1002/yea.1347
pubmed: 16498704
Janero DR (1990) Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 9:515–540. https://doi.org/10.1016/0891-5849(90)90131-2
doi: 10.1016/0891-5849(90)90131-2
pubmed: 2079232
Jiang X, Stockwell BR, Conrad M (2021) Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol 22:266–282. https://doi.org/10.1038/s41580-020-00324-8
doi: 10.1038/s41580-020-00324-8
pubmed: 33495651
pmcid: 8142022
Khan A, Singh P, Kumar R, Das S, Singh RK, Mina U, Agrswal GK, Rakwal R, Sarkar A, Srivastava A (2021) Antifungal activity of siderophore isolated from Escherichia coli against Aspergillus nidulans via iron-mediated oxidative stress. Front Microbiol 12:729032. https://doi.org/10.3389/fmicb.2021.729032
doi: 10.3389/fmicb.2021.729032
pubmed: 34803944
pmcid: 8596375
Kuhl I, Dujeancourt L, Gaisne M, Herbert CJ, Bonnefoy N (2011) A genome wide study in fission yeast reveals nine PPR proteins that regulate mitochondrial gene expression. Nucleic Acids Res 39:8029–8041. https://doi.org/10.1093/nar/gkr511
doi: 10.1093/nar/gkr511
pubmed: 21727087
pmcid: 3185421
Liang D, Minikes AM, Jiang X (2022) Ferroptosis at the intersection of lipid metabolism and cellular signaling. Mol Cell. https://doi.org/10.1016/j.molcel.2022.03.022
doi: 10.1016/j.molcel.2022.03.022
pubmed: 35390277
Lill R, Freibert SA (2020) Mechanisms of mitochondrial iron–sulfur protein biogenesis. Annu Rev Biochem 89:471–499. https://doi.org/10.1146/annurev-biochem-013118-111540
doi: 10.1146/annurev-biochem-013118-111540
pubmed: 31935115
Liu Z, Li Y, Xie W, Huang Y (2020) Schizosaccharomyces pombe Ppr10 is required for mitochondrial translation. FEMS Microbiol Lett. https://doi.org/10.1093/femsle/fnaa170
doi: 10.1093/femsle/fnaa170
pubmed: 33049028
Lu S, Wang J, Chitsaz F, Derbyshire MK, Geer RC, Gonzales NR, Gwadz M, Hurwitz DI, Marchler GH, Song JS, Thanki N, Yamashita RA, Yang M, Zhang D, Zheng C, Lanczycki CJ, Marchler-Bauer A (2020) CDD/SPARCLE: the conserved domain database in 2020. Nucleic Acids Res 48:D265–D268. https://doi.org/10.1093/nar/gkz991
doi: 10.1093/nar/gkz991
pubmed: 31777944
Luo Y, Wang Y, Huang Y (2021) Schizosaccharomyces pombe Ppr10 and Mpa1 together mediate mitochondrial translational initiation. J Biol Chem 297:100869. https://doi.org/10.1016/j.jbc.2021.100869
doi: 10.1016/j.jbc.2021.100869
pubmed: 34119521
pmcid: 8258696
Martinez AM, Kim A, Yang WS (2020) Detection of ferroptosis by BODIPY 581/591 C11. Methods Mol Biol 2108:125–130. https://doi.org/10.1007/978-1-0716-0247-8_11
doi: 10.1007/978-1-0716-0247-8_11
pubmed: 31939176
Misslinger M, Lechner BE, Bacher K, Haas H (2018) Iron-sensing is governed by mitochondrial, not by cytosolic iron–sulfur cluster biogenesis in Aspergillus fumigatus. Metallomics 10:1687–1700. https://doi.org/10.1039/c8mt00263k
doi: 10.1039/c8mt00263k
pubmed: 30395137
Mistry J, Chuguransky S, Williams L, Qureshi M, Salazar GA, Sonnhammer ELL, Tosatto SCE, Paladin L, Raj S, Richardson LJ, Finn RD, Bateman A (2021) Pfam: the protein families database in 2021. Nucleic Acids Res 49:D412–D419. https://doi.org/10.1093/nar/gkaa913
doi: 10.1093/nar/gkaa913
pubmed: 33125078
Morales M, Munne-Bosch S (2019) Malondialdehyde: facts and artifacts. Plant Physiol 180:1246–1250. https://doi.org/10.1104/pp.19.00405
doi: 10.1104/pp.19.00405
pubmed: 31253746
pmcid: 6752910
Moreno-Cermeno A, Obis E, Belli G, Cabiscol E, Ros J, Tamarit J (2010) Frataxin depletion in yeast triggers up-regulation of iron transport systems before affecting iron–sulfur enzyme activities. J Biol Chem 285:41653–41664. https://doi.org/10.1074/jbc.M110.149443
doi: 10.1074/jbc.M110.149443
pubmed: 20956517
pmcid: 3009893
Normant V, Mourer T, Labbe S (2018) The major facilitator transporter Str3 is required for low-affinity heme acquisition in Schizosaccharomyces pombe. J Biol Chem 293:6349–6362. https://doi.org/10.1074/jbc.RA118.002132
doi: 10.1074/jbc.RA118.002132
pubmed: 29549126
pmcid: 5925805
Park MW, Cha HW, Kim J, Kim JH, Yang H, Yoon S, Boonpraman N, Yi SS, Yoo ID, Moon JS (2021) NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer’s diseases. Redox Biol 41:101947. https://doi.org/10.1016/j.redox.2021.101947
doi: 10.1016/j.redox.2021.101947
pubmed: 33774476
pmcid: 8027773
Robert X, Gouet P (2014) Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res 42:W320-324. https://doi.org/10.1093/nar/gku316
doi: 10.1093/nar/gku316
pubmed: 24753421
pmcid: 4086106
Rovira AG, Smith AG (2019) PPR proteins: orchestrators of organelle RNA metabolism. Physiol Plant 166:451–459. https://doi.org/10.1111/ppl.12950
doi: 10.1111/ppl.12950
pubmed: 30809817
Shen Q, Liang M, Yang F, Deng YZ, Naqvi NI (2020) Ferroptosis contributes to developmental cell death in rice blast. New Phytol 227:1831–1846. https://doi.org/10.1111/nph.16636
doi: 10.1111/nph.16636
pubmed: 32367535
Su Y, Yang Y, Huang Y (2017) Loss of ppr3, ppr4, ppr6, or ppr10 perturbs iron homeostasis and leads to apoptotic cell death in Schizosaccharomyces pombe. FEBS J 284:324–337. https://doi.org/10.1111/febs.13978
doi: 10.1111/febs.13978
pubmed: 27886462
Tan JX, Finkel T (2020) Mitochondria as intracellular signaling platforms in health and disease. J Cell Biol. https://doi.org/10.1083/jcb.202002179
doi: 10.1083/jcb.202002179
pubmed: 32320464
pmcid: 7199861
Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680. https://doi.org/10.1093/nar/22.22.4673
doi: 10.1093/nar/22.22.4673
pubmed: 7984417
pmcid: 308517
UniProt C (2021) UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res 49:D480–D489. https://doi.org/10.1093/nar/gkaa1100
doi: 10.1093/nar/gkaa1100
Vakifahmetoglu-Norberg H, Ouchida AT, Norberg E (2017) The role of mitochondria in metabolism and cell death. Biochem Biophys Res Commun 482:426–431. https://doi.org/10.1016/j.bbrc.2016.11.088
doi: 10.1016/j.bbrc.2016.11.088
pubmed: 28212726
Wang Y, Yan J, Zhang Q, Ma X, Zhang J, Su M, Wang X, Huang Y (2017) The Schizosaccharomyces pombe PPR protein Ppr10 associates with a novel protein Mpa1 and acts as a mitochondrial translational activator. Nucleic Acids Res 45:3323–3340. https://doi.org/10.1093/nar/gkx127
doi: 10.1093/nar/gkx127
pubmed: 28334955
pmcid: 5389468
Zhang X, Krause KH, Xenarios I, Soldati T, Boeckmann B (2013) Evolution of the ferric reductase domain (FRD) superfamily: modularity, functional diversification, and signature motifs. PLoS ONE 8:e58126. https://doi.org/10.1371/journal.pone.0058126
doi: 10.1371/journal.pone.0058126
pubmed: 23505460
pmcid: 3591440