Apoptosis, Induced by Human α-Synuclein in Yeast, Can Occur Independent of Functional Mitochondria

Akintade, Damilare D.; Chaudhuri, Bhabatosh

doi:10.3390/cells9102203

Cited by 5 publications

(3 citation statements)

References 59 publications

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“…This function could also involve correcting the folding of misfolded proteins or preventing misfolding of proteins. Bax that delocalised from the cytosol to the mitochondria to exert its toxic effects may do so in a conformational form that is toxic for the cells (Akintade and Chaudhuri 2020a ). It may be that FKBP2 somehow prevents this toxic conformation of Bax from being formed.…”

Section: Resultsmentioning

confidence: 99%

FK506-binding protein 2 (FKBP13) inhibit Bax-induced apoptosis in Saccharomyces cerevisiae (yeast)

Akintade

Chaudhuri

2021

Cell Biol Toxicol

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FK506-binding protein 2 (FKBP13) is a part of the immunophilin protein family involved in immunoregulation. It is also believed to operate as a factor in membrane cytoskeletal framework and as an ER chaperone. FKBP2 (FKBP13) and FKBP1 (FKBP12), known as immunophilins, are binding proteins for rapamycin and FK506, which are immunosuppressive drugs. It was suggested that immunophilin-like and immunophilin proteins play significant roles in regulating intracellular calcium and protein folding/sorting, acting as molecular chaperones. Within the 15 mammalian FKBPs known, FKBP1 is merely the only one proven to form complexes with rapamycin and FK506 in the cytosol and facilitate their T cells immunosuppressive effects, FKBP2 is a luminal protein of the endoplasmic reticulum (ER) and is reported to take part in protein folding in the ER. However, little is known about FKBP2 link with apoptosis (either as a pro or anti-apoptotic protein). In this study, FKPB2 protein was co-expressed with the pro-apoptotic protein Bax after a yeast-based human hippocampal cDNA library screening. The yeast strain carrying the Bax gene was transformed with an episomal 2-micron plasmid that encodes the HA-tagged FKBP2 gene. The resultant strain would allow co-expression of Bax and FKBP2 in yeast cells. The results presented here show that a protein involved in protein folding can play a role in protecting yeast cell from Bax-induced apoptosis.

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Section: Resultsmentioning

confidence: 99%

FK506-binding protein 2 (FKBP13) inhibit Bax-induced apoptosis in Saccharomyces cerevisiae (yeast)

Akintade

Chaudhuri

2021

Cell Biol Toxicol

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“…JC-10 accumulates in the mitochondrial matrix and forms aggregates (J-aggregates) with red fluorescence in normal cells with high mitochondrial membrane potential. The membrane potential decreases in apoptotic cells, and JC-10 starts to diffuse out of the mitochondria, converting into a monomeric form (J-monomer) and emitting green fluorescence [86,87]. According to the results, a dose-dependent reduction in the mitochondrial membrane potential was observed after treating the HuTu 80 cells with the liposomal formulations.…”

Section: S2mentioning

confidence: 88%

Mitochondria-Targeted Lipid Nanoparticles Loaded with Rotenone as a New Approach for the Treatment of Oncological Diseases

Vasileva,

Gaynanova,

Kuznetsova

et al. 2023

Molecules

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This research is based on the concept that mitochondria are a promising target for anticancer therapy, including thatassociated with the use of oxidative phosphorylation blockers (mitochondrial poisons). Liposomes based on L-α-phosphatidylcholine (PC) and cholesterol (Chol) modified with cationic surfactants with triphenylphosphonium (TPPB-n, where n = 10, 12, 14, and 16) and imidazolium (IA-n(OH), where n = 10, 12, 14, and 16) head groups were obtained. The physicochemical characteristics of liposomes at different surfactant/lipid molar ratios were determined by dynamic/electrophoretic light scattering, transmission electron microscopy, and spectrophotometry. The hydrodynamic diameter of all the systems was within 120 nm with a polydispersity index of no more than 0.24 even after 2 months of storage. It was shown that cationization of liposomes leads to an increase in the internalization of nanocontainers in pancreatic carcinoma (PANC-1) and duodenal adenocarcinoma (HuTu 80) cells compared with unmodified liposomes. Also, using confocal microscopy, it was shown that liposomes modified with TPPB-14 and IA-14(OH) statistically better colocalize with the mitochondria of tumor cells compared with unmodified ones. At the next stage, the mitochondrial poison rotenone (ROT) was loaded into cationic liposomes. It was shown that the optimal loading concentration of ROT is 0.1 mg/mL. The Korsmeyer–Peppas and Higuchi kinetic models were used to describe the release mechanism of ROT from liposomes in vitro. A significant reduction in the IC50 value for the modified liposomes compared with free ROT was shown and, importantly, a higher degree of selectivity for the HuTu 80 cell line compared with the normal cells (SI value is 307 and 113 for PC/Chol/TPPB-14/ROT and PC/Chol/IA-14(OH)/ROT, respectively) occurred. It was shown that the treatment of HuTu 80 cells with ROT-loaded cationic liposomal formulations leads to a dose-dependent decrease in the mitochondrial membrane potential.

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“…The occurrence of apoptosis in yeast (Saccharomyces cerevisiae) is characterized by DNA fragmentation, plasma membrane blebbing, and cell shrinkage due to the reduction of cytoplasm and organelles (Julian and Olson, 2015). Dysfunction of cell organelles, especially mitochondria, can occur during the apoptosis process, affecting the morphology of yeast cells which causes the formation of petite colonies (Farrugia and Balzan, 2012;Akintade and Chaudhuri, 2020). The Yeast Caspase-1 (YCA1) protein activity induces the apoptosis mechanism in yeast.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis in Yeast is Modulated by Clove Leaf Extract and Eugenol Potentially by Interfering Caspase YCA1

Amini¹,

Astuti²,

Batubara³

2022

OnLine Journal of Biological Sciences

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Apoptosis is a process of cell death important for preventing the development of diseases such as cancer, neurodegenerative disorders, autoimmune, and cardiovascular disease. Apoptosis is reported to be potentially induced by antioxidant compounds, including phytoextract. Thus in this study, we determined the potential of apoptotic modulation in yeast cells by clove extract, which was rich in eugenol. Apoptotic in yeast (Saccharomyces cerevisiae) was observed by forming petite colonies. Molecular docking analysis was then performed to clarify the potential binding of eugenol towards yeast caspase YCA1, the key regulator of apoptosis in yeast. Our data indicate that clove leaf extract (500 ppm) increased the frequency of petite colonies by up to 94,2% in S. cerevisiae. Suggesting that the particular phytoextract induced the apoptosis phenomenon in yeast. The predominant compound in clove extract, eugenol, was capable to bind YCA1 with the affinity of -4, 4 kcal/moL. Thus it is suggested that the development of apoptotic yeast cells by clove phytoextract occurred potentially due to such direct regulation of eugenol towards YCA1. However, further in vivo studies are required to elucidate the mode of action of eugenol in the regulation of YCA1 activities.

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Apoptosis, Induced by Human α-Synuclein in Yeast, Can Occur Independent of Functional Mitochondria

Cited by 5 publications

References 59 publications

FK506-binding protein 2 (FKBP13) inhibit Bax-induced apoptosis in Saccharomyces cerevisiae (yeast)

FK506-binding protein 2 (FKBP13) inhibit Bax-induced apoptosis in Saccharomyces cerevisiae (yeast)

Mitochondria-Targeted Lipid Nanoparticles Loaded with Rotenone as a New Approach for the Treatment of Oncological Diseases

Apoptosis in Yeast is Modulated by Clove Leaf Extract and Eugenol Potentially by Interfering Caspase YCA1

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