{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:35:38Z","timestamp":1785418538920,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novartis Forschungsstiftung FreeNovation"},{"name":"OPO Foundation"},{"name":"Dementia Research, Synapsis Foundation Switzerland","award":["2022-PI05"],"award-info":[{"award-number":["2022-PI05"]}]},{"award":["2022-PI05"],"award-info":[{"award-number":["2022-PI05"]}],"id":[{"id":"https:\/\/ror.org\/03jrr8f73","id-type":"ROR","asserted-by":"publisher"}]},{"name":"B\u00fcrgenstock Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tauopathies are a group of neurodegenerative diseases characterized by the accumulation of abnormal tau protein, leading to mitochondrial dysfunction. Because of neurons\u2019 high energy demands, such impairments significantly contribute to neuronal vulnerability. Recent evidence indicates that mitochondria can be transferred between cells to support energy-deficient cells through intercellular mitochondrial transfer (IMT). Given the impact of pathological tau on mitochondrial transport and cytoskeletal dynamics, we hypothesized that IMT is altered in tauopathies. We investigated IMT from astrocytes to neurons, as well as the influence of abnormal tau protein on this process, using co-cultures of SH-SY5Y cells (neuronal model) and A172 cells (astrocytic model). Key data were then confirmed in human iPSC-derived neurons and astrocytes. We show that IMT is enhanced in the presence of abnormal tau and occurs predominantly through contact-dependent mechanisms. Transferred mitochondria were either integrated into the host mitochondrial network, degraded in lysosomes, or remained isolated in the recipient cells\u2019 cytosol. This transfer improved cellular respiration and was associated with increased bioenergetics in pathological cells. Together, our results highlight IMT as a link between tau pathology and neuronal metabolic adaptation, suggesting that this process reflects an endogenous metabolic adaptation holding therapeutic potential to mitigate energy deficits in neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/cells15121101","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T10:19:53Z","timestamp":1781691593000},"page":"1101","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Compensatory Intercellular Mitochondrial Transfer Improves Bioenergetics in P301L Tau-Affected Neuronal Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1056-1178","authenticated-orcid":false,"given":"Aur\u00e9lien","family":"Riou","sequence":"first","affiliation":[{"name":"Cell Biology & Energy Metabolism, University Psychiatric Clinics (UPK) Basel, University of Basel, 4002 Basel, Switzerland"},{"name":"Research Cluster Molecular and Cognitive Neurosciences, Department of Biomedicine, University of Basel, 4055 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Broeglin","sequence":"additional","affiliation":[{"name":"Cell Biology & Energy Metabolism, University Psychiatric Clinics (UPK) Basel, University of Basel, 4002 Basel, Switzerland"},{"name":"Research Cluster Molecular and Cognitive Neurosciences, Department of Biomedicine, University of Basel, 4055 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2210-9651","authenticated-orcid":false,"given":"Andreas","family":"Papassotiropoulos","sequence":"additional","affiliation":[{"name":"Research Cluster Molecular and Cognitive Neurosciences, Department of Biomedicine, University of Basel, 4055 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-3669","authenticated-orcid":false,"given":"Anne","family":"Eckert","sequence":"additional","affiliation":[{"name":"Neurobiology Laboratory for Brain Aging and Mental Health, University Psychiatric Clinics (UPK) Basel, University of Basel, 4002 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3323-1756","authenticated-orcid":false,"given":"Amandine","family":"Grimm","sequence":"additional","affiliation":[{"name":"Cell Biology & Energy Metabolism, University Psychiatric Clinics (UPK) Basel, University of Basel, 4002 Basel, Switzerland"},{"name":"Research Cluster Molecular and Cognitive Neurosciences, Department of Biomedicine, University of Basel, 4055 Basel, Switzerland"},{"name":"Neurobiology Laboratory for Brain Aging and Mental Health, University Psychiatric Clinics (UPK) Basel, University of Basel, 4002 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Szabo, L., Eckert, A., and Grimm, A. 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