AMPK Signaling Regulates Mitophagy and Mitochondrial ATP Production in Human Trophoblast Cell Line BeWo

Bin Wu, Yun Chen, Robert Clarke, Emmanuel Akala, Peixin Yang, Bin He, Haijun Gao

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Accumulating evidence suggests that mitochondrial structural and functional defects are present in human placentas affected by pregnancy related disorders, but mitophagy pathways in human trophoblast cells/placental tissues have not been investigated. Methods: In this study, we investigated three major mitophagy pathways mediated by PRKN, FUNDC1, and BNIP3/BNIP3L in response to AMPK activation by AICAR and knockdown of PRKAA1/2 (AKD) in human trophoblast cell line BeWo and the effect of AKD on mitochondrial membrane potential and ATP production. Results: Autophagy flux assay demonstrated that AMPK signaling activation stimulates autophagy, evidenced increased LC3II and SQSTM1 protein abundance in the whole cell lysates and mitochondrial fractions, and mitophagy flux assay demonstrated that the activation of AMPK signaling stimulates mitophagy via PRKN and FUNDC1 mediated but not BNIP3/BNIP3L mediated pathways. The stimulatory regulation of AMPK signaling on mitophagy was confirmed by AKD which reduced the abundance of LC3II, SQSTM1, PRKN, and FUNDC1 proteins, but increased the abundance of BNIP3/BNIP3L proteins. Coincidently, AKD resulted in elevated mitochondrial membrane potential and reduced mitochondrial ATP production, compared to control BeWo cells. Conclusions: In summary, AMPK signaling stimulates mitophagy in human trophoblast cells via PRKN and FUNDC1 mediated mitophagy pathways and AMPK regulated mitophagy contributes to the maintenance of mitochondrial membrane potential and mitochondrial ATP production.

Original languageEnglish (US)
Article number118
JournalFrontiers in Bioscience - Landmark
Volume27
Issue number4
DOIs
StatePublished - Apr 2022

Bibliographical note

Funding Information:
This research was funded by National Institutes of Health grants R03HD095417 (NICHD), U54MD007597 (NIMHD, Howard University RCMI Program), and Bridge Fund/Pilot Study Award (Dean’s Office Howard University College of Medicine).

Publisher Copyright:
© 2022 The Author(s).

Keywords

  • AMPK
  • ATP production
  • BeWo
  • human
  • mitochondria
  • mitophagy
  • trophoblast

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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