Apoptosis, Induced by Human α-Synuclein in Yeast, Can Occur Independent of Functional Mitochondria
Human α-synuclein expression in baker’s yeast reportedly induces mitochondria-dependent apoptosis. Surprisingly, we find that, under de-repressing conditions of the inducible <i>MET25/GAL1</i> promoters, yeast cells expressing chromosomally-integrated copies of the human α-synuclein gene...
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MDPI AG
2020-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/10/2203 |
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| author | Damilare D. Akintade Bhabatosh Chaudhuri |
| author_facet | Damilare D. Akintade Bhabatosh Chaudhuri |
| author_sort | Damilare D. Akintade |
| collection | DOAJ |
| description | Human α-synuclein expression in baker’s yeast reportedly induces mitochondria-dependent apoptosis. Surprisingly, we find that, under de-repressing conditions of the inducible <i>MET25/GAL1</i> promoters, yeast cells expressing chromosomally-integrated copies of the human α-synuclein gene are not killed, but spontaneously form respiration-deficient rho-minus (ρ<sup>−</sup>) petites. Although yeast cells can undergo cell death (apoptosis) from loss of mitochondrial function, they can also survive without functional mitochondria. Such cells are referred to as ρ<sup>0</sup> or ρ<sup>−</sup> petites. This study reports that minimal expression of human α-synuclein in yeast, from <i>MET25</i>/<i>GAL1</i> promoter, gives rise to ρ<sup>−</sup> petites. Interestingly, the full expression of α-synuclein, from the same promoters, in α-synuclein-triggered ρ<sup>−</sup> petites and also in ρ<sup>0</sup> petites (produced by treating ρ<sup>+</sup> cells with the mutagen ethidium bromide) initiates apoptosis. The percentages of petites increase with increasing α-synuclein gene copy-number. ρ<sup>−</sup> petites expressing α-synuclein from fully-induced <i>MET25</i>/<i>GAL1</i> promoters exhibit increased ROS levels, loss of mitochondrial membrane potential, and nuclear DNA fragmentation, with increasing copies of α-synuclein. Our results indicate that, for the first time in yeast, α-synuclein-triggered apoptosis can occur independently of functional mitochondria. The observation that α-synuclein naturally forms petites and that they can undergo apoptosis may have important implications in understanding the pathogenesis of Parkinson’s disease. |
| first_indexed | 2024-03-10T15:58:16Z |
| format | Article |
| id | doaj.art-d39c67df3e744d80ae67e3b0d33df1bc |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T15:58:16Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d39c67df3e744d80ae67e3b0d33df1bc2023-11-20T15:30:36ZengMDPI AGCells2073-44092020-09-01910220310.3390/cells9102203Apoptosis, Induced by Human α-Synuclein in Yeast, Can Occur Independent of Functional MitochondriaDamilare D. Akintade0Bhabatosh Chaudhuri1School of Life Sciences, Medical School, University of Nottingham, Nottingham NG7 2UH, UKLeicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UKHuman α-synuclein expression in baker’s yeast reportedly induces mitochondria-dependent apoptosis. Surprisingly, we find that, under de-repressing conditions of the inducible <i>MET25/GAL1</i> promoters, yeast cells expressing chromosomally-integrated copies of the human α-synuclein gene are not killed, but spontaneously form respiration-deficient rho-minus (ρ<sup>−</sup>) petites. Although yeast cells can undergo cell death (apoptosis) from loss of mitochondrial function, they can also survive without functional mitochondria. Such cells are referred to as ρ<sup>0</sup> or ρ<sup>−</sup> petites. This study reports that minimal expression of human α-synuclein in yeast, from <i>MET25</i>/<i>GAL1</i> promoter, gives rise to ρ<sup>−</sup> petites. Interestingly, the full expression of α-synuclein, from the same promoters, in α-synuclein-triggered ρ<sup>−</sup> petites and also in ρ<sup>0</sup> petites (produced by treating ρ<sup>+</sup> cells with the mutagen ethidium bromide) initiates apoptosis. The percentages of petites increase with increasing α-synuclein gene copy-number. ρ<sup>−</sup> petites expressing α-synuclein from fully-induced <i>MET25</i>/<i>GAL1</i> promoters exhibit increased ROS levels, loss of mitochondrial membrane potential, and nuclear DNA fragmentation, with increasing copies of α-synuclein. Our results indicate that, for the first time in yeast, α-synuclein-triggered apoptosis can occur independently of functional mitochondria. The observation that α-synuclein naturally forms petites and that they can undergo apoptosis may have important implications in understanding the pathogenesis of Parkinson’s disease.https://www.mdpi.com/2073-4409/9/10/2203human α-synucleinmitochondria-dependentmitochondria-independentyeast petitesyeast apoptosis |
| spellingShingle | Damilare D. Akintade Bhabatosh Chaudhuri Apoptosis, Induced by Human α-Synuclein in Yeast, Can Occur Independent of Functional Mitochondria Cells human α-synuclein mitochondria-dependent mitochondria-independent yeast petites yeast apoptosis |
| title | Apoptosis, Induced by Human α-Synuclein in Yeast, Can Occur Independent of Functional Mitochondria |
| title_full | Apoptosis, Induced by Human α-Synuclein in Yeast, Can Occur Independent of Functional Mitochondria |
| title_fullStr | Apoptosis, Induced by Human α-Synuclein in Yeast, Can Occur Independent of Functional Mitochondria |
| title_full_unstemmed | Apoptosis, Induced by Human α-Synuclein in Yeast, Can Occur Independent of Functional Mitochondria |
| title_short | Apoptosis, Induced by Human α-Synuclein in Yeast, Can Occur Independent of Functional Mitochondria |
| title_sort | apoptosis induced by human α synuclein in yeast can occur independent of functional mitochondria |
| topic | human α-synuclein mitochondria-dependent mitochondria-independent yeast petites yeast apoptosis |
| url | https://www.mdpi.com/2073-4409/9/10/2203 |
| work_keys_str_mv | AT damilaredakintade apoptosisinducedbyhumanasynucleininyeastcanoccurindependentoffunctionalmitochondria AT bhabatoshchaudhuri apoptosisinducedbyhumanasynucleininyeastcanoccurindependentoffunctionalmitochondria |