Role of apoptosis-inducing factors in oxidative defense and assembly of respiration complexes

Apoptosis-inducing factors (AIFs) are a conserved family of NADH oxidoreductases. First, AIFs are N-terminally anchored in the inner mitochondrial membrane functioning in oxidative phosphorylation and detoxification. Partially they are necessary for the efficient assembly of
respiration complex I and III and antioxidant defence. Apoptotic stimuli induce cleavage of AIFs, which migrate to
the nucleus, induce DNA degradation and lead to apoptosis.

Previous investigations in the four AIF homologues PaAif1,
PaAif2, PaAmid1 and PaAmid2 in the filamentous fungus Podospora anserina resulted in a mitochondrial localisation of PaAIF2-GFP and PaAMID2-GFP. Additionally PaAIF2-GFP translocates from mitochondria to the nucleus. ΔPaAif2 and ΔPaAmid2 showed increased stress tolerance and lifespan extension (Brust et al. 2010).

To exclude the redundant function of the four AIF homologues, two double deletions ΔPaAmid1/Aif1
and ΔPaAmid2/Aif2 and a deletion of all four ΔPaAmid1/2/Aif1/2 were generated. Lifespan, influence on the assembly of respiration complexes, behaviour under different stressors, generation of H₂O₂ and catalase activity were examined. Lifespan of ΔPaAmid2/Aif2 and ΔPaAmid1/2/Aif1/2 is extended and their respiration complexes show partially different intensities and an additional signal on BN-PAGE. No difference in catalase
activity was observed, but ΔPaAmid1/2/Aif1/2 generates
less H₂O₂.