The Haves and Have-Nots: The Mitochondrial Permeability Transition Pore across Species
The demonstration that F<sub>1</sub>F<sub>O</sub> (F)-ATP synthase and adenine nucleotide translocase (ANT) can form Ca<sup>2+</sup>-activated, high-conductance channels in the inner membrane of mitochondria from a variety of eukaryotes led to renewed interest in...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/12/10/1409 |
| _version_ | 1797600620771803136 |
|---|---|
| author | Elena Frigo Ludovica Tommasin Giovanna Lippe Michela Carraro Paolo Bernardi |
| author_facet | Elena Frigo Ludovica Tommasin Giovanna Lippe Michela Carraro Paolo Bernardi |
| author_sort | Elena Frigo |
| collection | DOAJ |
| description | The demonstration that F<sub>1</sub>F<sub>O</sub> (F)-ATP synthase and adenine nucleotide translocase (ANT) can form Ca<sup>2+</sup>-activated, high-conductance channels in the inner membrane of mitochondria from a variety of eukaryotes led to renewed interest in the permeability transition (PT), a permeability increase mediated by the PT pore (PTP). The PT is a Ca<sup>2+</sup>-dependent permeability increase in the inner mitochondrial membrane whose function and underlying molecular mechanisms have challenged scientists for the last 70 years. Although most of our knowledge about the PTP comes from studies in mammals, recent data obtained in other species highlighted substantial differences that could be perhaps attributed to specific features of F-ATP synthase and/or ANT. Strikingly, the anoxia and salt-tolerant brine shrimp <i>Artemia franciscana</i> does not undergo a PT in spite of its ability to take up and store Ca<sup>2+</sup> in mitochondria, and the anoxia-resistant <i>Drosophila melanogaster</i> displays a low-conductance, selective Ca<sup>2+</sup>-induced Ca<sup>2+</sup> release channel rather than a PTP. In mammals, the PT provides a mechanism for the release of cytochrome <i>c</i> and other proapoptotic proteins and mediates various forms of cell death. In this review, we cover the features of the PT (or lack thereof) in mammals, yeast, <i>Drosophila melanogaster</i>, <i>Artemia franciscana</i> and <i>Caenorhabditis elegans</i>, and we discuss the presence of the intrinsic pathway of apoptosis and of other forms of cell death. We hope that this exercise may help elucidate the function(s) of the PT and its possible role in evolution and inspire further tests to define its molecular nature. |
| first_indexed | 2024-03-11T03:50:25Z |
| format | Article |
| id | doaj.art-1fc58a2a946f4dd3be7ffb5b4bf43762 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T03:50:25Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1fc58a2a946f4dd3be7ffb5b4bf437622023-11-18T00:53:12ZengMDPI AGCells2073-44092023-05-011210140910.3390/cells12101409The Haves and Have-Nots: The Mitochondrial Permeability Transition Pore across SpeciesElena Frigo0Ludovica Tommasin1Giovanna Lippe2Michela Carraro3Paolo Bernardi4Department of Biomedical Sciences and CNR Neuroscience Institute, University of Padova, Via Ugo Bassi 58/B, I-35131 Padova, ItalyDepartment of Biomedical Sciences and CNR Neuroscience Institute, University of Padova, Via Ugo Bassi 58/B, I-35131 Padova, ItalyDepartment of Medicine, University of Udine, Piazzale Kolbe 4, I-33100 Udine, ItalyDepartment of Biomedical Sciences and CNR Neuroscience Institute, University of Padova, Via Ugo Bassi 58/B, I-35131 Padova, ItalyDepartment of Biomedical Sciences and CNR Neuroscience Institute, University of Padova, Via Ugo Bassi 58/B, I-35131 Padova, ItalyThe demonstration that F<sub>1</sub>F<sub>O</sub> (F)-ATP synthase and adenine nucleotide translocase (ANT) can form Ca<sup>2+</sup>-activated, high-conductance channels in the inner membrane of mitochondria from a variety of eukaryotes led to renewed interest in the permeability transition (PT), a permeability increase mediated by the PT pore (PTP). The PT is a Ca<sup>2+</sup>-dependent permeability increase in the inner mitochondrial membrane whose function and underlying molecular mechanisms have challenged scientists for the last 70 years. Although most of our knowledge about the PTP comes from studies in mammals, recent data obtained in other species highlighted substantial differences that could be perhaps attributed to specific features of F-ATP synthase and/or ANT. Strikingly, the anoxia and salt-tolerant brine shrimp <i>Artemia franciscana</i> does not undergo a PT in spite of its ability to take up and store Ca<sup>2+</sup> in mitochondria, and the anoxia-resistant <i>Drosophila melanogaster</i> displays a low-conductance, selective Ca<sup>2+</sup>-induced Ca<sup>2+</sup> release channel rather than a PTP. In mammals, the PT provides a mechanism for the release of cytochrome <i>c</i> and other proapoptotic proteins and mediates various forms of cell death. In this review, we cover the features of the PT (or lack thereof) in mammals, yeast, <i>Drosophila melanogaster</i>, <i>Artemia franciscana</i> and <i>Caenorhabditis elegans</i>, and we discuss the presence of the intrinsic pathway of apoptosis and of other forms of cell death. We hope that this exercise may help elucidate the function(s) of the PT and its possible role in evolution and inspire further tests to define its molecular nature.https://www.mdpi.com/2073-4409/12/10/1409mitochondriapermeability transitionATP synthaseadenine nucleotide translocasechannelscalcium signaling |
| spellingShingle | Elena Frigo Ludovica Tommasin Giovanna Lippe Michela Carraro Paolo Bernardi The Haves and Have-Nots: The Mitochondrial Permeability Transition Pore across Species Cells mitochondria permeability transition ATP synthase adenine nucleotide translocase channels calcium signaling |
| title | The Haves and Have-Nots: The Mitochondrial Permeability Transition Pore across Species |
| title_full | The Haves and Have-Nots: The Mitochondrial Permeability Transition Pore across Species |
| title_fullStr | The Haves and Have-Nots: The Mitochondrial Permeability Transition Pore across Species |
| title_full_unstemmed | The Haves and Have-Nots: The Mitochondrial Permeability Transition Pore across Species |
| title_short | The Haves and Have-Nots: The Mitochondrial Permeability Transition Pore across Species |
| title_sort | haves and have nots the mitochondrial permeability transition pore across species |
| topic | mitochondria permeability transition ATP synthase adenine nucleotide translocase channels calcium signaling |
| url | https://www.mdpi.com/2073-4409/12/10/1409 |
| work_keys_str_mv | AT elenafrigo thehavesandhavenotsthemitochondrialpermeabilitytransitionporeacrossspecies AT ludovicatommasin thehavesandhavenotsthemitochondrialpermeabilitytransitionporeacrossspecies AT giovannalippe thehavesandhavenotsthemitochondrialpermeabilitytransitionporeacrossspecies AT michelacarraro thehavesandhavenotsthemitochondrialpermeabilitytransitionporeacrossspecies AT paolobernardi thehavesandhavenotsthemitochondrialpermeabilitytransitionporeacrossspecies AT elenafrigo havesandhavenotsthemitochondrialpermeabilitytransitionporeacrossspecies AT ludovicatommasin havesandhavenotsthemitochondrialpermeabilitytransitionporeacrossspecies AT giovannalippe havesandhavenotsthemitochondrialpermeabilitytransitionporeacrossspecies AT michelacarraro havesandhavenotsthemitochondrialpermeabilitytransitionporeacrossspecies AT paolobernardi havesandhavenotsthemitochondrialpermeabilitytransitionporeacrossspecies |