PMID- 35722364
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 10
IP  - 10
DP  - 2022 May
TI  - Mitochondria-specific peptide amphiphiles induce mitochondrial dysfunction and 
      peripheral T-cell lymphomas (PTCL) damage.
PG  - 570
LID - 10.21037/atm-22-2233 [doi]
LID - 570
AB  - BACKGROUND: Peripheral T-cell lymphomas (PTCL) are aggressive lymphomas with poor 
      prognosis, and therefore, there is a pressing need to explore new targets or 
      compounds. Mitochondria may serve as a potential therapeutic target for PTCL. A 
      designed positively-charged segment (pKV) is anchored to the specific 15 amino 
      acid sequence (MIASHLLAYFFTELN) to yield a cell-penetrating peptide (pHK-pKV) and 
      a lipid chain (Pal) is conjugated to the N-terminus of pHK-pKV (Pal-pHK-pKV) are 
      bioactive amphiphilic peptide assemblies targeting the interaction between 
      mitochondrial voltage dependent anion channel 1 (VDAC1) and hexokinase II (HKII). 
      METHODS: PTCL cell line H9 was treated with Pal-pHK-pKV and pHK-pKV, 
      respectively. Cell proliferation in each group was measured by detecting cell 
      viability and the corresponding marker Ki-67. Apoptosis was detected by 
      immunofluorescence, flow cytometry and western blot. We also measured 
      mitochondrial membrane potential, adenosine triphosphate (ATP) production, the 
      cytochrome c distribution and the expression levels of B cell lymphoma 2 (BCL-2) 
      and BCL-2 associated X protein (BAX). Western blot was used to detect the 
      activation of the extracellular regulated protein kinases (ERK) signaling 
      pathway. RESULTS: Pal-pHK-pKV and pHK-pKV with 20 microM blocked the interaction 
      between VDAC1 and HKII, and detached HKII from mitochondria, which depolarized 
      the mitochondrial membrane potential, induced mitochondria dysfunction, and 
      decreased ATP production. The decreased ATP subsequently inhibited the activation 
      of the ERK/BCL-2 pathway and increased the BAX/BCL-2 ratio. Cytochrome c was then 
      released from the mitochondria and induced capase-3 activation and subsequently 
      apoptosis. Additionally, decreased ATP induced the expression of FAS and then 
      apoptosis. CONCLUSIONS: Mitochondria specific peptide amphiphiles induce 
      mitochondrial dysfunction and provide a new approach for the treatment of PTCL.
CI  - 2022 Annals of Translational Medicine. All rights reserved.
FAU - Sun, Qi
AU  - Sun Q
AD  - Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, 
      Fudan University, Shanghai, China.
FAU - Gui, Ailing
AU  - Gui A
AD  - Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, 
      Fudan University, Shanghai, China.
FAU - Zou, Aihua
AU  - Zou A
AD  - College of Chemistry and Materials Science, Shanghai Normal University, Shanghai, 
      China.
FAU - Yan, Yichen
AU  - Yan Y
AD  - Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, 
      Fudan University, Shanghai, China.
FAU - Qiu, Shi
AU  - Qiu S
AD  - Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, 
      Fudan University, Shanghai, China.
FAU - Zhu, Shun
AU  - Zhu S
AD  - Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, 
      Fudan University, Shanghai, China.
FAU - Liu, Wen
AU  - Liu W
AD  - Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, 
      Fudan University, Shanghai, China.
FAU - Zuo, Ji
AU  - Zuo J
AD  - Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, 
      Fudan University, Shanghai, China.
FAU - Zhang, Qunling
AU  - Zhang Q
AD  - Department of Lymphoma, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Yang, Ling
AU  - Yang L
AD  - Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, 
      Fudan University, Shanghai, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC9201132
OTO - NOTNLM
OT  - Amphiphilic peptides
OT  - apoptosis
OT  - mitochondrial dysfunction
OT  - peripheral T-cell lymphoma (PTCL)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://atm.amegroups.com/article/view/10.21037/atm-22-2233/coif). The authors 
      have no conflicts of interest to declare.
EDAT- 2022/06/21 06:00
MHDA- 2022/06/21 06:01
PMCR- 2022/05/01
CRDT- 2022/06/20 04:07
PHST- 2022/03/29 00:00 [received]
PHST- 2022/05/17 00:00 [accepted]
PHST- 2022/06/20 04:07 [entrez]
PHST- 2022/06/21 06:00 [pubmed]
PHST- 2022/06/21 06:01 [medline]
PHST- 2022/05/01 00:00 [pmc-release]
AID - atm-10-10-570 [pii]
AID - 10.21037/atm-22-2233 [doi]
PST - ppublish
SO  - Ann Transl Med. 2022 May;10(10):570. doi: 10.21037/atm-22-2233.