The Mitochondrial Dnm1-Like Fission Component Is Required for lga2 -Induced Mitophagy but Dispensable for Starvation-Induced Mitophagy in Ustilago maydis

Abstract

Selective elimination of mitochondria by autophagy (mitophagy) is a crucial developmental process to dispose of disintegrated or superflous organelles. However, little is known about underlying regulatory mechanisms. We have investigated mitophagy in response to conditional overexpression of the a2 mating-type locus gene lga2, which encodes a small mitochondrial protein critically involved in uniparental mitochondrial DNA inheritance during sexual development of Ustilago maydis. In this study, we show that conditional overexpression of lga2 efficiently triggers mitophagy that is dependent on atg8 and atg11, consistent with selective autophagy. lga2-triggered mitophagy is preceded by mitochondrial dysfunction, including depletion of mitochondrial RNA transcripts, and is mechanistically distinct from starvation-induced mitophagy despite a common requirement for atg11. In particular, lga2-triggered mitophagy strongly depends on the mitochondrial fission factor Dnm1, but it is only slightly affected by N-acetylcysteine, which is an inhibitor of starvation-induced mitophagy. To further delineate the role of mitochondrial fission, we analyzed lga2 effects in ⌬fis1 mutants. This revealed that mitochondrial fragmentation was only attenuated and mitophagy was largely unaffected. In further support of a Fis1-independent role for Dnm1, mitochondrial association of green fluorescent protein-tagged Dnm1 as well as Dnm1-opposed mitochondrial fusion during sexual development were fis1 independent. In conclusion, our results specify the role of the mitochondrial fission factor Dnm1 in mitophagy and uncover differences between mitophagy pathways in the same cellular system.

Differential Expression of Genes Related to Mitochondrial Biogenesis and Bioenergetics in Fatigued Prostate Cancer Men Receiving External Beam Radiation Therapy

“…39 Inhibition of fission using an ex vivo Fis1 knockdown model showed an accumulation of damaged mitochondrial material, decreased metabolic function, and reduction in insulin secretion. 40 The differential expressions of these four genes ( BCL2L1, BCS1L, SLC25A37, FIS1) suggest that mitochondrial autophagy and processes involving iron synthesis or storage might be associated with the changes in fatigue symptoms experienced by the study subjects.…”

Origins of Eukaryotic Sexual Reproduction

“…Finally, deletion of rga2 from a2 cells results in loss of the a2 mitochondrial genome and inheritance of mitochondria from the a1 parent-exactly the opposite of the pattern observed with wild-type crosses. Thus rga2 protects the host cell mitochondrial genome, whereas lga2 functions in mitochondrial destruction via a dynamin-dependent mitophagy pathway (Mahlert et al 2009;Nieto-Jacobo et al 2012).…”

Current perspectives on mitochondrial inheritance in fungi

“…42 In both C. neoformans and U. maydis, there is increasing evidence for selective degradation of mtDNA from one parent at an early stage of sexual mating. 35,43 However, the genes and molecular processes that mark the mitochondria from the different parents for inheritance or targeted elimination, either before or during mating, remain to be determined.…”