Mitochondria are positioned at dendritic branch induction sites, a process requiring rhotekin2 and syndapin I

Abstract Proper neuronal development, function and survival critically rely on mitochondrial functions. Yet, how developing neurons ensure spatiotemporal distribution of mitochondria during expansion of their dendritic arbor remained unclear. We demonstrate the existence of effective mitochondrial p...

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Main Authors: Jessica Tröger, Regina Dahlhaus, Anne Bayrhammer, Dennis Koch, Michael M. Kessels, Britta Qualmann
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-57399-0
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author Jessica Tröger
Regina Dahlhaus
Anne Bayrhammer
Dennis Koch
Michael M. Kessels
Britta Qualmann
author_facet Jessica Tröger
Regina Dahlhaus
Anne Bayrhammer
Dennis Koch
Michael M. Kessels
Britta Qualmann
author_sort Jessica Tröger
collection DOAJ
description Abstract Proper neuronal development, function and survival critically rely on mitochondrial functions. Yet, how developing neurons ensure spatiotemporal distribution of mitochondria during expansion of their dendritic arbor remained unclear. We demonstrate the existence of effective mitochondrial positioning and tethering mechanisms during dendritic arborization. We identify rhotekin2 as outer mitochondrial membrane-associated protein that tethers mitochondria to dendritic branch induction sites. Rhotekin2-deficient neurons failed to correctly position mitochondria at these sites and also lacked the reduction in mitochondrial dynamics observed at wild-type nascent dendritic branch sites. Rhotekin2 hereby serves as important anchor for the plasma membrane-binding and membrane curvature-inducing F-BAR protein syndapin I (PACSIN1). Consistently, syndapin I loss-of-function phenocopied the rhotekin2 loss-of-function phenotype in mitochondrial positioning at dendritic branch induction sites. The finding that rhotekin2 deficiency impaired dendritic branch induction and that a syndapin binding-deficient rhotekin2 mutant failed to rescue this phenotype highlighted the physiological importance of rhotekin2 functions for neuronal network formation.
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issn 2041-1723
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spelling doaj-art-b2ef6584a4e7491391b5cb870310a4772025-08-20T02:10:13ZengNature PortfolioNature Communications2041-17232025-03-0116112310.1038/s41467-025-57399-0Mitochondria are positioned at dendritic branch induction sites, a process requiring rhotekin2 and syndapin IJessica Tröger0Regina Dahlhaus1Anne Bayrhammer2Dennis Koch3Michael M. Kessels4Britta Qualmann5Institute of Biochemistry I, Jena University Hospital - Friedrich Schiller University JenaInstitute of Biochemistry I, Jena University Hospital - Friedrich Schiller University JenaInstitute of Biochemistry I, Jena University Hospital - Friedrich Schiller University JenaInstitute of Biochemistry I, Jena University Hospital - Friedrich Schiller University JenaInstitute of Biochemistry I, Jena University Hospital - Friedrich Schiller University JenaInstitute of Biochemistry I, Jena University Hospital - Friedrich Schiller University JenaAbstract Proper neuronal development, function and survival critically rely on mitochondrial functions. Yet, how developing neurons ensure spatiotemporal distribution of mitochondria during expansion of their dendritic arbor remained unclear. We demonstrate the existence of effective mitochondrial positioning and tethering mechanisms during dendritic arborization. We identify rhotekin2 as outer mitochondrial membrane-associated protein that tethers mitochondria to dendritic branch induction sites. Rhotekin2-deficient neurons failed to correctly position mitochondria at these sites and also lacked the reduction in mitochondrial dynamics observed at wild-type nascent dendritic branch sites. Rhotekin2 hereby serves as important anchor for the plasma membrane-binding and membrane curvature-inducing F-BAR protein syndapin I (PACSIN1). Consistently, syndapin I loss-of-function phenocopied the rhotekin2 loss-of-function phenotype in mitochondrial positioning at dendritic branch induction sites. The finding that rhotekin2 deficiency impaired dendritic branch induction and that a syndapin binding-deficient rhotekin2 mutant failed to rescue this phenotype highlighted the physiological importance of rhotekin2 functions for neuronal network formation.https://doi.org/10.1038/s41467-025-57399-0
spellingShingle Jessica Tröger
Regina Dahlhaus
Anne Bayrhammer
Dennis Koch
Michael M. Kessels
Britta Qualmann
Mitochondria are positioned at dendritic branch induction sites, a process requiring rhotekin2 and syndapin I
Nature Communications
title Mitochondria are positioned at dendritic branch induction sites, a process requiring rhotekin2 and syndapin I
title_full Mitochondria are positioned at dendritic branch induction sites, a process requiring rhotekin2 and syndapin I
title_fullStr Mitochondria are positioned at dendritic branch induction sites, a process requiring rhotekin2 and syndapin I
title_full_unstemmed Mitochondria are positioned at dendritic branch induction sites, a process requiring rhotekin2 and syndapin I
title_short Mitochondria are positioned at dendritic branch induction sites, a process requiring rhotekin2 and syndapin I
title_sort mitochondria are positioned at dendritic branch induction sites a process requiring rhotekin2 and syndapin i
url https://doi.org/10.1038/s41467-025-57399-0
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