Co-expression of Mcl-1 and Bak induces mitochondrial swelling

  • Biochem Biophys Res Commun. 2020 Jul 5;527(4):866-873. doi: 10.1016/j.bbrc.2020.04.154.
Yong Wang  1 ,  Wenhua Su  1 ,  Zihao Mai  1 ,  Mengyan Du  1 ,  Si Yu  1 ,  Yangpei Liu  1 ,  Xiaopin Wang  2 ,  Tongshen Chen  3
Affiliations
  • 1. MOE Key Laboratory & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.
  • 2. Department of Pain Management, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China. Electronic address: [email protected].
  • 3. MOE Key Laboratory & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China. Electronic address: [email protected].
PMID: 32430171 DOI: 10.1016/j.bbrc.2020.04.154
Abstract

We here used fluorescence imaging to explore the effect of co-overexpression of Mcl-1 and Bak/BH3-only proteins on mitochondrial morphology. The cells co-expressing CFP-Mcl-1 and YFP-Bak/BimL/Puma/tBid showed co-localization of Mcl-1 with Bak/Puma/BimL/tBid and also showed the inhibitory action of Mcl-1 on the Bak-, BimL-, Puma- or tBid-mediated cell death. Co-expression of Mcl-1 and Bak but not BH3-only proteins induced time-dependent mitochondrial swelling. Fluorescence resonance energy transfer (FRET) imaging proved the direct binding of Mcl-1 to Bak, BimL, Puma and tBid, respectively. In addition, Mcl-1 prevented Bak oligomerization by retrotranslocating Bak from mitochondria into cytoplasm. Moreover, Mcl-1-Bak complex exhibited a good co-localization with mitochondria, and co-expression of Mcl-1 and Bak for more than 24 h not only induced mitochondrial swelling but also impaired mitochondrial membrane potential. Collectively, co-expression of Mcl-1 and Bak but not BH3-only proteins significantly induced mitochondrial swelling and subsequent loss of mitochondrial membrane potential.

Keywords
BH3-only proteins; Bak; Fluorescence imaging; Mcl-1; Mitochondrial swelling.
Products