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Dengler, L.* ; Padovani, F. ; Lemke, B.* ; Brugger, R.* ; Benedikt, A. ; Westermann, B.* ; Maček, B.* ; Schmoller, K.M. ; Ewald, J.C.*

In the absence of mitochondrial fusion unequal segregation of mitochondria drives mtDNA loss.

EMBO Rep., DOI: 10.1038/s44319-026-00794-5 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Mitochondrial biogenesis and inheritance must be tightly coordinated with cell division to maintain mitochondrial function and cell survival. The dynamics of the mitochondrial network, including fusion and fission, are essential for mitochondrial inheritance and quality control. In budding yeast, simultaneous inhibition of both processes compromises mitochondrial DNA (mtDNA) integrity, increasing the frequency of petite cells. Loss of fusion alone completely eliminates mtDNA. Although this has been known for decades, why mtDNA is lost remained unclear. Here, we examine the effects of impaired mitochondrial fusion by depleting the mitofusin Fzo1. By analyzing over thirty thousand single cells across their cell cycles, we show that Fzo1-depletion induces rapid mitochondrial fragmentation and loss of membrane potential, followed by progressive declines in mtDNA content and growth rate. During division, Fzo1-depleted daughters inherit disproportionately large mitochondrial amounts, leaving mothers with too little. This imbalance, combined with an inability to upregulate compensatory mtDNA synthesis, drives rapid mtDNA loss. Our results reveal how fusion defects cause mtDNA loss and mitochondrial dysfunction, which might have implications for diseases linked to impaired fusion.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Mitochondrial Dna ; Mitochondrial Fusion ; Mitochondrion ; Mitochondrial Biogenesis ; Non-mendelian Inheritance ; Dnaja3 ; Cell Fusion ; Fragmentation (computing) ; Biogenesis; Yeast; Fission; Genome; Inheritance; Protein; Gtpase; Cells; Expression; Integrity; Lacking
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Journal EMBO Reports
Publisher Springer
Publishing Place Campus, 4 Crinan St, London, N1 9xw, England
Reviewing status Peer reviewed
Institute(s) Institute of Functional Epigenetics (IFE)
Grants Deutsche Forschungsgemeinschaft (DFG)