DnmA and FisA Mediate Mitochondria and Peroxisome Fission, and Regulate Mitochondrial Function, ROS Production and Development in Aspergillus nidulans.

Verónica Garrido-Bazán,Jesús Aguirre,Juan Pablo Pardo

doi:10.3389/fmicb.2020.00837

Verónica Garrido-Bazán, Jesús Aguirre + Show 1 more

Open Access

https://doi.org/10.3389/fmicb.2020.00837

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Abstract

The dynamin-like protein Drp1 and its receptor Fis-1 are required for mitochondria and peroxisome fission in animal and yeast cells. Here, we show that in the fungus Aspergillus nidulans the lack of Drp1 and Fis-1 homologs DnmA and FisA has strong developmental defects, leading to a notable decrease in hyphal growth and asexual and sexual sporulation, with some of these defects being aggravated or partially remediated by different carbon sources. Although both DnmA and FisA, are essential for mitochondrial fission, participate in peroxisomal division and are fully required for H2O2-induced mitochondrial division, they also appear to play differential functions. Despite their lack of mitochondrial division, ΔdnmA and ΔfisA mutants segregate mitochondria to conidiogenic cells and produce viable conidia that inherit a single mitochondrion. During sexual differentiation, ΔdnmA and ΔfisA mutants develop fruiting bodies (cleistothecia) that differentiate excessive ascogenous tissue and a reduced number of viable ascospores. ΔdnmA and ΔfisA mutants show decreased respiration and notably high levels of mitochondrial reactive oxygen species (ROS), which likely correspond to superoxide. Regardless of this, ΔdnmA mutants can respond to an external H2O2 challenge by re-localizing the MAP kinase-activated protein kinase (MAPKAP) SrkA from the cytoplasm to the nuclei. Our results show that ROS levels regulate mitochondrial dynamics while a lack of mitochondrial fission results in lower respiration, increased mitochondrial ROS and developmental defects, indicating that ROS, mitochondrial division and development are critically interrelated processes.

Highlights

Our work has been oriented to demonstrate that reactive oxygen species (ROS) play critical signaling roles in cell differentiation (Hansberg and Aguirre, 1990; Aguirre et al, 2005; Mendoza-Martinez et al, 2017; Mendoza-Martínez et al, 2019)
As we have previously shown that H2O2 induces mitochondrial fragmentation in A. nidulans (Jaimes-Arroyo et al, 2015), we wanted to test if DnmA and FisA were required for such stress response, as well as for normal mitochondrial division
Our results show that A. nidulans growing hyphal tips contain mitochondria that are mostly organized as filamentous networks

Summary

Introduction

Our work has been oriented to demonstrate that ROS play critical signaling roles in cell differentiation (Hansberg and Aguirre, 1990; Aguirre et al, 2005; Mendoza-Martinez et al, 2017; Mendoza-Martínez et al, 2019). During the course of that work, we found that the MAPKAP-kinase SrkA is part of this pathway and that in response to external H2O2 it translocates from the cytoplasm to either the nucleus or the mitochondria, depending on the presence of the upstream MAPK SakA. Under these conditions, mitochondria underwent extensive fragmentation, consistent with the induction of mitochondrial division by H2O2 (Jaimes-Arroyo et al, 2015). The lack of mitochondrial fission results in mice embryonic lethality (Wakabayashi et al, 2009) and several human pathologies are related to defects in mitochondrial dynamics (Poole et al, 2008; Trevisan et al, 2018)

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