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Updated: Dec 20, 2025
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Published on: May 2, 2025
DnmA and FisA Mediate Mitochondria and Peroxisome Fission, and Regulate Mitochondrial Function, ROS Production and
Verónica Garrido-Bazán1,2, Juan Pablo Pardo3, Jesús Aguirre1
1Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
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.
Insights
Mitochondrial division proteins DnmA and FisA are crucial for fungal development and respiration in Aspergillus nidulans. Their absence causes defects, increased ROS, and altered development, highlighting the link between mitochondrial dynamics, ROS, and growth.
Area of Science:
- Cell Biology
- Mycology
- Genetics
Background:
- Dynamin-like protein 1 (Drp1) and its receptor, Mitochondrial fission 1 (Fis-1), are key regulators of organelle division in eukaryotes.
- These proteins are essential for mitochondrial and peroxisome fission in animal and yeast cells.
- The roles of Drp1 and Fis-1 homologs in filamentous fungi, like Aspergillus nidulans, remain less understood.
Purpose of the Study:
- To investigate the function of DnmA (Drp1 homolog) and FisA (Fis-1 homolog) in the fungus Aspergillus nidulans.
- To determine the impact of DnmA and FisA on mitochondrial and peroxisomal division, cellular respiration, and development.
- To explore the relationship between mitochondrial dynamics, reactive oxygen species (ROS), and developmental processes in A. nidulans.
Main Methods:
- Generation and phenotypic analysis of deletion mutants for DnmA (ΔdnmA) and FisA (ΔfisA) in Aspergillus nidulans.
- Microscopic examination of mitochondria and peroxisomes, assessing their morphology and distribution.
- Measurement of cellular respiration, reactive oxygen species (ROS) levels, and evaluation of developmental stages (hyphal growth, sporulation, sexual differentiation).
Main Results:
- Deletion of DnmA and FisA resulted in significant developmental defects, including reduced hyphal growth and impaired asexual and sexual sporulation.
- Both DnmA and FisA are essential for mitochondrial fission and involved in peroxisomal division; however, they exhibit differential functions.
- Mutants displayed decreased respiration, elevated mitochondrial ROS (superoxide), and altered sexual development, with DnmA mutants showing a specific response to H2O2 challenge.
Conclusions:
- Mitochondrial dynamics, regulated by ROS levels, are critical for fungal development in A. nidulans.
- Loss of mitochondrial fission leads to reduced respiration, increased mitochondrial ROS, and developmental abnormalities.
- ROS, mitochondrial division, and fungal development are intricately interconnected processes.
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