Investigation of the role of cardiolipin on autophagy in the yeast model


Öz Arslan D. , Kılıçkaya G., Bilge,Bilge B., Üstüner B., Kılınç E. , Kan B. , et al.

41st FEBS Congress, Molecular and Systems Biology for a Better Life, Aydın, Türkiye, 3 - 08 August 2016, cilt.283, ss.1-441

  • Cilt numarası: 283
  • Basıldığı Şehir: Aydın
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayısı: ss.1-441

Özet

Cardiolipin (CL) is a phospholipid which is localized exclusively to the mitochondrial inner membrane (MIM). CL interacts with proteins involved in oxidative phosphorylation and also plays a role in the modulation of apoptosis and autophagy. We studied the role of CL on autophagy/mitophagy, in two mutant strains of S. cerevisiae, the Crd1Δ (cardiolipin synthase gene deleted) strain and the Taz1Δ (Tafazzin, a critical cardiolipin modifying enzyme gene deleted) strain and the wild-type S. cerevisiae strain GA74-1A. Autophagy induction was monitored by GFP expression using Western blot and flow cytometric analyses. We observed that autophagy induction increased in three strains which were grown in different media. Mitochondrial respiration, mitochondrial membrane potential and the organization of mitochondrial protein complexes were also studied. In the wild-type strain, while autophagy did not affect NADH-dependent mitochondrial respiration significantly, it positively affects succinatedependent respiration. In contrast, in the Taz1Δ strain, autophagy negatively affects succinate-dependent respiration. We found that levels of complex IV subunit Cox2p changed in the in Crd1Δ strain upon starvation. Measurement of mitochondrial membrane potential (MMP) showed a decrease in Crd1Δ strain grown in fermentative and non-fermentative media. Prolonged autophagy induction diminished the level of MMP in all strains. In addition, mRNA levels of Atg32 and Atg17 that are essential proteins for mitophagy showed different profile in wild-type and mutant yeast strains. We further analysed changes in lipid composition of mitochondria upon autophagy induction. The data presented in this study on the possible roles of cardiolipin in autophagy and mitophagy will contribute to the understanding of the basic mechanisms of aging and neurodegenerative disorders. Acknowledgement: This work was supported by The Scientific And Technological Research Council Of Turkey (Grant number: 212T027).