Loss of Num1-mediated cortical dynein anchoring negatively impacts respiratory growth

Authors

Antoineen J. White, Northwestern University
Clare S. Harper, Northwestern University
Erica M. Rosario, Northwestern University
Jonathan V. Dietz, University of Nebraska-Lincoln
Hannah G. Addis, College of Charleston
Jennifer L. Fox, College of Charleston
Oleh Khalimonchuk, University of Nebraska-LincolnFollow
Laura L. Lackner, Northwestern University

Document Type

Article

Date of this Version

9-26-2022

Citation

Journal of Cell Science (2022) 135, jcs259980. doi:10.1242/jcs.259980

Comments

Used by permission.

Abstract

Num1 is a multifunctional protein that both tethers mitochondria to the plasma membrane and anchors dynein to the cell cortex during nuclear inheritance. Previous work has examined the impact loss of Num1-based mitochondrial tethering has on dynein function in Saccharomyces cerevisiae; here, we elucidate its impact on mitochondrial function. We find that like mitochondria, Num1 is regulated by changes in metabolic state, with the protein levels and cortical distribution of Num1 differing between fermentative and respiratory growth conditions. In cells lacking Num1, we observe a reproducible respiratory growth defect, suggesting a role for Num1 in not only maintaining mitochondrial morphology, but also function. A structure–function approach revealed that, unexpectedly, Num1- mediated cortical dynein anchoring is important for normal growth under respiratory conditions. The severe respiratory growth defect in Δnum1 cells is not specifically due to the canonical functions of dynein in nuclear migration but is dependent on the presence of dynein, as deletion of DYN1 in Δnum1 cells partially rescues respiratory growth. We hypothesize that misregulated dynein present in cells that lack Num1 negatively impacts mitochondrial function resulting in defects in respiratory growth.