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bioRxiv · 10.1101/2025.11.20.689567

Tom70-mediated mitochondria-nuclear envelope contacts regulate nuclear pore complex inheritance during gametogenesis

Ruediger, C. T.·Styler, B. S.·Sawyer, E. S.·Spiri, S.·King, G. A.·Walsh, M. E.·Brar, G. A.·Jorgens, D. M.·Ünal, E.
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Abstract

Gametogenesis rejuvenates the cellular lineage and excludes senescence-associated factors from gametes. In Saccharomyces cerevisiae, this involves sequestration of nuclear constituents into the Gametogenesis-Uninherited Nuclear Compartment (GUNC), which is excluded from gametes. Here we identify the conserved mitochondrial import receptor Tom70 as a key regulator of GUNC-mediated exclusion. Loss of TOM70 disrupts the sequestration of nuclear pore complexes, but not senescence-associated aggregates and nucleolar components, into the GUNC. Tom70s role appears independent of its canonical function in mitochondrial import and instead reflects a meiosis-specific requirement for mitochondria-nuclear envelope tethering. During meiosis II, Tom70 concentrates around the GUNC, where it recruits the nuclear envelope tethering protein Cnm1. Loss of CNM1 partially phenocopies tom70{Delta}, consistent with parallel tethering interactions. These findings uncover a previously unrecognized organelle contact-dependent pathway that remodels the nuclear envelope to support selective nuclear inheritance. More broadly, they highlight how organelle contacts integrate with nuclear quality control to safeguard gamete integrity.

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Ruediger, C. T., Styler, B. S., Sawyer, E. S., Spiri, S., King, G. A., Walsh, M. E., Brar, G. A., Jorgens, D. M., Ünal, E.. 2025-11-21. Tom70-mediated mitochondria-nuclear envelope contacts regulate nuclear pore complex inheritance during gametogenesis. https://doi.org/10.1101/2025.11.20.689567

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