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Kadam, Ashlesha, Mehta, Darshan, Jubin, Tina, Mansuri, MS Mohmmad Shoab, Begum, Rasheedunnisa, (2020) ' Apoptosis inducing factor: Cellular protective function in Dictyostelium discoideum. ' Biochim Biophys Acta Bioenerg 148158
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Abstract:Apoptosis Inducing Factor (AIF), a nuclear encoded mitochondrial inter-membrane space flavoprotein with intrinsic NADH oxidase activity, plays an important role in inducing cell death mechanisms. In response to cell death signals, it undergoes mitochondrio-nuclear translocation leading to DNA fragmentation. In addition to its role in cell death, AIF has a pro-survival role, wherein it contributes to the maintenance of mitochondrial structure and function in a coordinated manner. However, its exact mechanism of controlling mitochondrial homeostasis is unclear. The current study aims to explore the protective functions of AIF by its downregulation and overexpression in Dictyostelium discoideum. Constitutive AIF downregulated (dR) cells exhibited compromised oxidative phosphorylation along with elevated levels of cellular ROS. Interestingly, constitutive AIF dR cells showed amelioration in the activity of the ETC complexes upon antioxidant treatment, strengthening AIF's role as a ROS regulator, by virtue of its oxidoreductase property. Also, constitutive AIF dR cells showed lower transcript levels of the various subunits of ETC. Moreover, loss of AIF affected mtDNA content and mitochondrial fusion-fission mechanism which subsequently caused morphometric mitochondrial alterations. Constitutive AIF overexpressed (OE) cells also showed higher cellular ROS and mitochondrial fission genes transcript levels along with reduced mitochondrial fusion genes transcript levels and mtDNA content. Thus, the results of the current study provide a paradigm where AIF is implicated in cell survival by maintaining mitochondrial bioenergetics, morphology and fusion-fission mechanism in D. discoideum, an evolutionarily significant model organism for mitochondrial diseases.
Status: aheadofprint Type: Journal article Source: PUBMED PubMed ID: 31991113

Genes addressed in this paper
aif atp6 cluA cox1/2 cytB dymA dymB fszA
Topics in this paper
Transcriptional Regulation
Strains/Constructs X

Regulatory Role X

Regulated By
Mutants/Phenotypes X

Function/Process X

Genes addressed in this paper
fszB nad1 nad6 nad9 ndufa5 ndufa9
Topics in this paper
Transcriptional Regulation X X X X X X

Regulatory Role

Regulated By X X X X X X