bims-miptne 2024-12-08 papers

Parasitol Res. 2024 Dec 04. 123(12): 404

The cyclophilin D (CypD) of Toxoplasma gondii is involved in the parasite's response to oxidative stress damage.

Zhu Ying, Yihan Wu, Zhepeng Sun, Jing Liu, Qun Liu.

The mitochondrial permeability transition pore (mPTP) significantly impacts mitochondrial responses to cell death signals through its structural opening. Cyclophilin D (CypD) serves as a key regulator of the mPTP and plays a pivotal role in governing mitochondrial responses to cell death. In this study, we have demonstrated that Toxoplasma expresses a homolog of cyclophilin D, named TgCypD, which is localized in the mitochondria. Depletion of TgCypD resulted in a modest inhibition of tachyzoite invasion and proliferation, with no notable effect on mitochondrial morphology. However, TgCypD deficiency led to the inhibition of cytochrome c release from mitochondria into the cytosol, thereby imparting resistance to oxidative stress-induced cell death. Our findings suggest that T. gondii contains the mPTP component protein TgCypD, which is intricately involved in regulating mitochondrial responses to cell death.

Keywords: Toxoplasma gondii ; Cyclophilin D; Mitochondrial permeability transition pore (mPTP); Oxidative stress damage response

DOI: https://doi.org/10.1007/s00436-024-08412-w

Biochim Biophys Acta Bioenerg. 2024 Nov 29. pii: S0005-2728(24)00498-5. [Epub ahead of print]1866(1): 149528

Inside-out submitochondrial particles affect the mitochondrial permeability transition pore opening under conditions of mitochondrial dysfunction.

Cristina Algieri, Antonia Cugliari, Patrycja Anna Glogowski, Silvia Granata, Micaela Fabbri, Fabiana Trombetti, Maria Laura Bacci, Salvatore Nesci.

The inside-out submitochondrial particles (IO-SMPs) showed a strong protective effect against mitochondrial permeability transition pore (mPTP) opening in mitochondria isolated from swine hearts 3 h after explantation. The latter condition was used to emulate situation of mitochondrial damage. We identified that the protective effect of IO-SMPs cannot be attributed to a functional modulation of the enzymatic complexes involved in mPTP formation. Indeed, oxidative phosphorylation and F1FO-ATPase activity were not affected. Conversely, mPTP desensitization might be caused by structural modification. IO-SMP incorporation into the mitochondria can modulate the membrane-bound enzyme complexes' functionality, inducing F1FO-ATPase to be unable to carry out the conformational changes useful for mPTP opening. Thus, the data are a valid starting point for IO-SMP application in the treatment of impaired cardiovascular conditions supported by mPTP opening.

Keywords: F(1)F(O)-ATPase; Inside-out submitochondrial particles; Mitochondrial dysfunction; Mitochondrial permeability transition pore

DOI: https://doi.org/10.1016/j.bbabio.2024.149528

J Mol Histol. 2024 Dec 04. 56(1): 30

Involvement of necroptosıs and apoptosıs ın protectıve effects of cyclosporın a on ischemıa-reperfusıon injury in rat kıdney.

Zeynep Erdogmus Ozgen, Meral Erdinc, Meryem Seyda Kaya, Fesih Aktar, Selver Ozsener Ozekinci, Levent Erdinc, Emre Uyar.

We aimed to investigate the protective effects of low dose cyclosporin A (CsA) on ischemia-reperfusion (IR) injury in rat the kidney and on the apoptotic and necroptotic mechanisms involved. 1. Control group (received a single intraperitoneal (i.p.) dose of 1 ml sterile saline 15 min before the surgical procedure), 2. IR group (was subjected to 30 min of bilateral kidney ischemia followed by 90 min of reperfusion; and received a single i.p. dose of 1 ml sterile saline 15 min before the IR procedure, 3. IR + CsA group (received a single i.p. dose of 3 mg/kg CsA 15 min before the IR procedure. Renal functions (renal perfusion pressures, and serum urea-creatinine levels), kidney histological scores, MDA levels, and TNF-α, caspase-3, RIP1, RIP3, MLKL, CaMKII and CypD protein expressions were also measured. Renal perfusion pressures (PP), serum urea and creatinine levels, renal tissue MDA levels, and the protein expression levels of TNF-α, caspase-3, RIP1, RIP3, MLKL, CAMKII and CypD were significantly increased in the IR group compared to the control group (p < 0.05), Additionally, there were significant decreases in all the parameters in the IR + CsA group compared to those in the IR group (p < 0.05). Furthermore, histopathological analyses revealed significantly higher kidney injury scores in the IR group compared to the control group, and low dose CsA treatment improved the injury. A single low dose of CsA injection 15 min before IR, demonstrated a protective effect on bilateral renal IR injury and a reduction in apoptotic and necroptopic markers which is resulted in improvement of renal functions.

Keywords: CAMKII; Caspase-3; CypD; Low dose cyclosporin A (CsA); MLKL; RIP1; RIP3; Renal ischemia–reperfusion (IR); Renal perfusion pressure; TNF-α

DOI: https://doi.org/10.1007/s10735-024-10281-7