1. Academic Validation
  2. Anti-apoptotic capacity of Mcl-1Δ127

Anti-apoptotic capacity of Mcl-1Δ127

  • Biochem Biophys Res Commun. 2020 Jun 11;526(4):1042-1048. doi: 10.1016/j.bbrc.2020.03.181.
Yong Wang 1 Wenhua Su 1 Zihao Mai 1 Si Yu 1 Xiaoping Wang 2 Tongsheng Chen 3
Affiliations

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: txp2938@jnu.edu.cn.
  • 3 MOE Key Laboratory & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China. Electronic address: chentsh@scnu.edu.cn.
Abstract

The anti-apoptotic ability of Mcl-1Δ127, a Caspase cleavage product of Mcl-1, is debated. We here used fluorescence imaging to assess the anti-apoptotic capacity of Mcl-1Δ127 in living cells. Fluorescence imaging of living cells expressing CFP-Mcl-1Δ127 showed that Mcl-1Δ127 existed mainly in cytoplasm. Fluorescence imaging of living cells co-expressing CFP-Mcl-1Δ127 and YFP-Bak, CFP-Mcl-1Δ127 and YFP-BimL, CFP-Mcl-1Δ127 and YFP-Puma or CFP-Mcl-1Δ127 and YFP-tBid showed that Mcl-1Δ127 markedly inhibited the oligomerization of Bak, BimL, Puma and tBid on mitochondria and also inhibited the Bak-, BimL-, Puma- or tBid-mediated cell death, resulting in their partial localization in cytoplasm. Fluorescence resonance energy transfer (FRET) imaging proved that Mcl-1Δ127 bound to Bak, BimL, Puma and tBid, respectively. Fluorescence loss in photobleaching (FLIP) analyses showed that Mcl-1Δ127 did prevent Bak oligomerization by retrotranslocating Bak from mitochondria into cytoplasm. Collectively, Mcl-1Δ127 has the same anti-apoptotic capacity as Mcl-1, and prevents Apoptosis by sequestering BH3-only or Bak proteins, thus inhibiting their oligomerization on mitochondria.

Keywords

Apoptosis; BH3-only proteins; Bak; Fluorescence imaging; Mcl-1Δ127.

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