Alterations of Mitochondrial Structure in Methamphetamine Toxicity
Recent evidence shows that methamphetamine (METH) produces mitochondrial alterations that contribute to neurotoxicity. Nonetheless, most of these studies focus on mitochondrial activity, whereas mitochondrial morphology remains poorly investigated. In fact, morphological evidence about the fine stru...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/8926 |
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| author | Paola Lenzi Francesca Biagioni Carla L. Busceti Gloria Lazzeri Maico Polzella Alessandro Frati Michela Ferrucci Francesco Fornai |
| author_facet | Paola Lenzi Francesca Biagioni Carla L. Busceti Gloria Lazzeri Maico Polzella Alessandro Frati Michela Ferrucci Francesco Fornai |
| author_sort | Paola Lenzi |
| collection | DOAJ |
| description | Recent evidence shows that methamphetamine (METH) produces mitochondrial alterations that contribute to neurotoxicity. Nonetheless, most of these studies focus on mitochondrial activity, whereas mitochondrial morphology remains poorly investigated. In fact, morphological evidence about the fine structure of mitochondria during METH toxicity is not available. Thus, in the present study we analyzed dose-dependent mitochondrial structural alterations during METH exposure. Light and transmission electron microscopy were used, along with ultrastructural stoichiometry of catecholamine cells following various doses of METH. In the first part of the study cell death and cell degeneration were assessed and they were correlated with mitochondrial alterations observed using light microscopy. In the second part of the study, ultrastructural evidence of specific mitochondrial alterations of crests, inner and outer membranes and matrix were quantified, along with in situ alterations of mitochondrial proteins. Neurodegeneration induced by METH correlates significantly with specific mitochondrial damage, which allows definition of a scoring system for mitochondrial integrity. In turn, mitochondrial alterations are concomitant with a decrease in fission/mitophagy protein Fis1 and DRP1 and an increase in Pink1 and Parkin in situ, at the mitochondrial level. These findings provide structural evidence that mitochondria represent both direct and indirect targets of METH-induced toxicity. |
| first_indexed | 2024-03-09T04:21:15Z |
| format | Article |
| id | doaj.art-c099ff7fece44b74aa8d3bf7da10e36a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:21:15Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c099ff7fece44b74aa8d3bf7da10e36a2023-12-03T13:47:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316892610.3390/ijms23168926Alterations of Mitochondrial Structure in Methamphetamine ToxicityPaola Lenzi0Francesca Biagioni1Carla L. Busceti2Gloria Lazzeri3Maico Polzella4Alessandro Frati5Michela Ferrucci6Francesco Fornai7Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, ItalyIstituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via Atinense 18, 86077 Pozzilli, ItalyIstituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via Atinense 18, 86077 Pozzilli, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, ItalyAliveda Laboratories, Viale Karol Wojtyla, 19, 56042 Crespina Lorenzana, ItalyIstituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Via Atinense 18, 86077 Pozzilli, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, ItalyRecent evidence shows that methamphetamine (METH) produces mitochondrial alterations that contribute to neurotoxicity. Nonetheless, most of these studies focus on mitochondrial activity, whereas mitochondrial morphology remains poorly investigated. In fact, morphological evidence about the fine structure of mitochondria during METH toxicity is not available. Thus, in the present study we analyzed dose-dependent mitochondrial structural alterations during METH exposure. Light and transmission electron microscopy were used, along with ultrastructural stoichiometry of catecholamine cells following various doses of METH. In the first part of the study cell death and cell degeneration were assessed and they were correlated with mitochondrial alterations observed using light microscopy. In the second part of the study, ultrastructural evidence of specific mitochondrial alterations of crests, inner and outer membranes and matrix were quantified, along with in situ alterations of mitochondrial proteins. Neurodegeneration induced by METH correlates significantly with specific mitochondrial damage, which allows definition of a scoring system for mitochondrial integrity. In turn, mitochondrial alterations are concomitant with a decrease in fission/mitophagy protein Fis1 and DRP1 and an increase in Pink1 and Parkin in situ, at the mitochondrial level. These findings provide structural evidence that mitochondria represent both direct and indirect targets of METH-induced toxicity.https://www.mdpi.com/1422-0067/23/16/8926neurotoxicitypsychostimulantsMitoTrackerultrastructural morphometrymitochondrial fissionmitophagy |
| spellingShingle | Paola Lenzi Francesca Biagioni Carla L. Busceti Gloria Lazzeri Maico Polzella Alessandro Frati Michela Ferrucci Francesco Fornai Alterations of Mitochondrial Structure in Methamphetamine Toxicity International Journal of Molecular Sciences neurotoxicity psychostimulants MitoTracker ultrastructural morphometry mitochondrial fission mitophagy |
| title | Alterations of Mitochondrial Structure in Methamphetamine Toxicity |
| title_full | Alterations of Mitochondrial Structure in Methamphetamine Toxicity |
| title_fullStr | Alterations of Mitochondrial Structure in Methamphetamine Toxicity |
| title_full_unstemmed | Alterations of Mitochondrial Structure in Methamphetamine Toxicity |
| title_short | Alterations of Mitochondrial Structure in Methamphetamine Toxicity |
| title_sort | alterations of mitochondrial structure in methamphetamine toxicity |
| topic | neurotoxicity psychostimulants MitoTracker ultrastructural morphometry mitochondrial fission mitophagy |
| url | https://www.mdpi.com/1422-0067/23/16/8926 |
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