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Genetic studies have identified 19 monogenic mutations\u2014accounting for ~10% of PD cases\u2014that affect mitochondrial function and are associated with early- or late-onset PD. Early-onset forms typically involve genes encoding proteins essential for mitochondrial quality control, including mitophagy and structural maintenance, while late-onset mutations impair mitochondrial dynamics, bioenergetics, and trafficking. Atypical juvenile genetic syndromes also exhibit mitochondrial abnormalities. In idiopathic PD, environmental neurotoxins such as pesticides and MPTP act as mitochondrial inhibitors, disrupting complex I activity and increasing reactive oxygen species. These converging pathways underscore mitochondria as a central node in PD pathology. This review explores the overlapping and distinct mitochondrial mechanisms in genetic and non-genetic PD, emphasizing their role in neuronal vulnerability. Targeting mitochondrial dysfunction finally offers a promising therapeutic avenue to slow or modify disease progression by intervening at a key point of neurodegenerative convergence.<\/jats:p>","DOI":"10.3390\/ijms26094451","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T11:46:19Z","timestamp":1746618379000},"page":"4451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Mitochondrial Dysfunction in Genetic and Non-Genetic Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8825-142X","authenticated-orcid":false,"given":"Martina","family":"Lucchesi","sequence":"first","affiliation":[{"name":"Department of Biology, University of Pisa, 56127 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8401-4615","authenticated-orcid":false,"given":"Letizia","family":"Biso","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Bonaso","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biancamaria","family":"Longoni","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0954-5384","authenticated-orcid":false,"given":"Bianca","family":"Buchignani","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy"},{"name":"Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7889-1355","authenticated-orcid":false,"given":"Roberta","family":"Battini","sequence":"additional","affiliation":[{"name":"Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo Maria","family":"Santorelli","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-8253","authenticated-orcid":false,"given":"Stefano","family":"Doccini","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Scarselli","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1136\/practneurol-2013-000741","article-title":"Non-Motor Parkinson\u2019s: Integral to Motor Parkinson\u2019s, yet Often Neglected","volume":"14","author":"Todorova","year":"2014","journal-title":"Pract. 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