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Neurological disorders depending on impaired mitochondrial function or homeostasis can be caused by the misregulation of \u201cendogenous players\u201d, such as nuclear or cytoplasmic regulators, which have been treated elsewhere. In this review, we focus on how exogenous agents, i.e., viral pathogens, or unbalanced microbiota in the gut-brain axis can also endanger mitochondrial dynamics in the central nervous system (CNS). Neurotropic viruses such as Herpes, Rabies, West-Nile, and Polioviruses seem to hijack neuronal transport networks, commandeering the proteins that mitochondria typically use to move along neurites. However, several neurological complications are also associated to infections by pandemic viruses, such as Influenza A virus and SARS-CoV-2 coronavirus, representing a relevant risk associated to seasonal flu, coronavirus disease-19 (COVID-19) and \u201cLong-COVID\u201d. Emerging evidence is depicting the gut microbiota as a source of signals, transmitted via sensory neurons innervating the gut, able to influence brain structure and function, including cognitive functions. Therefore, the direct connection between intestinal microbiota and mitochondrial functions might concur with the onset, progression, and severity of CNS diseases.<\/jats:p>","DOI":"10.3390\/biom13010169","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T02:29:55Z","timestamp":1673836195000},"page":"169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Exogenous Players in Mitochondria-Related CNS Disorders: Viral Pathogens and Unbalanced Microbiota in the Gut-Brain Axis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9887-0044","authenticated-orcid":false,"given":"Irene","family":"Righetto","sequence":"first","affiliation":[{"name":"Synthetic Biology and Biotechnology Unit, Department of Biology, University of Padua, via Ugo Bassi, 58\/B, 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4933-2578","authenticated-orcid":false,"given":"Matteo","family":"Gasparotto","sequence":"additional","affiliation":[{"name":"Synthetic Biology and Biotechnology Unit, Department of Biology, University of Padua, via Ugo Bassi, 58\/B, 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2557-0443","authenticated-orcid":false,"given":"Laura","family":"Casalino","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics \u201cA. Buzzati Traverso\u201d, CNR, via Pietro Castellino, 111, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5495-9183","authenticated-orcid":false,"given":"Marcella","family":"Vacca","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics \u201cA. Buzzati Traverso\u201d, CNR, via Pietro Castellino, 111, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5672-0726","authenticated-orcid":false,"given":"Francesco","family":"Filippini","sequence":"additional","affiliation":[{"name":"Synthetic Biology and Biotechnology Unit, Department of Biology, University of Padua, via Ugo Bassi, 58\/B, 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/sj.cdd.4401577","article-title":"Cell Death in HIV Dementia","volume":"12","author":"Mattson","year":"2005","journal-title":"Cell Death Differ."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gasparotto, M., Lee, Y.-S., Palazzi, A., Vacca, M., and Filippini, F. (2022). 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