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

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 H 2 O 2-induced mitochondrial division, they also appear to play differential functions. Despite their lack of mitochondrial division, dnmA and fisA mutants segregate mitochondria to conidiogenic cells and produce viable conidia that inherit a single mitochondrion. During sexual differentiation, dnmA and fisA mutants develop fruiting bodies (cleistothecia) that differentiate excessive ascogenous tissue and a reduced number of viable ascospores. dnmA and fisA mutants show decreased respiration and notably high levels of mitochondrial reactive oxygen species (ROS), which likely correspond to superoxide. Regardless of this, dnmA mutants can respond to an external H 2 O 2 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.

Dynamic Regulation of Peroxisomes and Mitochondria during Fungal Development

“…Mutants of the peroxisome-mitochondrial fission machinery in fungi generally have alterations in mycelial growth; although, the extent of these alterations can vary among species, and depending on the available nutrients, denoting different contributions of the fission machinery in hyphal growth [ 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 ]. Moreover, the morphology of mitochondria and peroxisomes in mutants defective for the mitochondrial-peroxisome fission proteins can also vary.…”

“…Asexual sporulation in most studied fungi is disturbed by defects in the peroxisome-mitochondrial fission machinery. The elimination of proteins of the fission machinery results in decreased conidia formation in diverse ascomycete fungi, differing in their lifestyle and evolutionary lineage, including the blast rice fungus Magnaporthe oryzae [ 105 , 108 , 110 ], the human pathogen A. fumigatus [ 104 ], the saprophytic A. nidulans [ 100 , 101 ] and the entomopathogenic Metarhizium robertsii [ 107 ]. Likewise, the formation of the different asexual spores—i.e., conidia and blastospores—produced by entomopathogen Beauveria bassiana is also affected by the elimination of Dnm1, Fis1, or Mdv1 [ 106 ].…”

“…In some of these fungi, like M. oryzae [ 110 ] and A. nidulans [ 100 ], these conidiation deficiencies are associated with a reduced number of conidiophores and a decrease in the number of spores produced per conidiophore. In contrast, in B. bassiana conidiation appears to be only delayed [ 106 ], indicating different contributions for the peroxisome-mitochondria fission machinery to fungal conidiation.…”

“…In contrast, in B. bassiana conidiation appears to be only delayed [ 106 ], indicating different contributions for the peroxisome-mitochondria fission machinery to fungal conidiation. Of interest, despite these conidiation deficiencies, mitochondria can be segregated into conidia in Aspergilli even when the fission proteins are absent [ 100 , 104 ]. Likewise, albeit microconidia in P. anserina rather function as male gametes during the sexual cycle (also known as spermatia), the segregation of mitochondria into these specialized conidia is also not affected upon loss of Fis1 or Dnm1 [ 102 ].…”

“…There remains ambiguity about the precise contribution of the fission machinery to conidiation. Evidence from Aspergilli support a decreased mitochondrial respiratory activity when the peroxisome-mitochondrial fission machinery is absent [ 100 , 104 ], and a moderate reduction of mycelial ATP generation occurs after Fis1, Mdv1 , or Dnm1 deletion in B. bassiana [ 106 ], suggesting that a reduced generation of energy in mitochondria contribute to the conidiation defects of the fission mutants. Mitochondria and peroxisomes constitute an important source for ROS in the cell.…”