Carnitine palmitoyltransferase 1C contributes to progressive cellular senescence

Yongtao Wang, Tao Yu, Yanying Zhou, Shike Wang, Xunian Zhou, Limin Wang, Tianmiao Ou, Yixin Chen, Yawen Zhou, Huizhen Zhang, Ying Wang, Xiaomei Fan, Pan Chen, Frank J. Gonzalez, Aiming Yu, Peng Huang, Min Huang, Huichang Bi

Research output: Contribution to journalArticle

Abstract

Stable transfection manipulation with antibiotic selection and passaging induces progressive cellular senescence phenotypes. However, the underlying mechanisms remain poorly understood. This study demonstrated that stable transfection of the empty vector induced PANC-1 cells into cellular senescence. Metabolomics revealed several acylcarnitines and their upstream regulatory gene, carnitine palmitoyltransferase 1C (CPT1C) involved in fatty acid β-oxidation in mitochondria, were strikingly decreased in senescent PANC-1 cells. Low CPT1C expression triggered mitochondrial dysfunction, inhibited telomere elongation, impaired cell survival under metabolic stress, and hindered the malignance and tumorigenesis of senescent cells. On the contrary, mitochondrial activity was restored by CPT1C gain-of-function in senescent vector PANC-1 cells. PPARα and TP53/CDKN1A, crucial signaling components in cellular senescence, were downregulated in senescent PANC-1 cells. This study identifies CPT1C as a key regulator of stable transfection-induced progressive PANC-1 cell senescence that inhibits mitochondrial function-associated metabolic reprogramming. These findings confirm the need to identify cell culture alterations after stable transfection, particularly when cells are used for metabolomics and mitochondria-associated studies, and suggest inhibition of CPT1C could be a promising target to intervene pancreatic tumorigenesis.

Original languageEnglish (US)
Pages (from-to)6733-6755
Number of pages23
JournalAging
Volume12
Issue number8
DOIs
StatePublished - Apr 14 2020

Keywords

  • carnitine palmitoyltransferase 1C
  • metabolic reprogramming
  • mitochondria
  • senescence
  • stable transfection

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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  • Cite this

    Wang, Y., Yu, T., Zhou, Y., Wang, S., Zhou, X., Wang, L., Ou, T., Chen, Y., Zhou, Y., Zhang, H., Wang, Y., Fan, X., Chen, P., Gonzalez, F. J., Yu, A., Huang, P., Huang, M., & Bi, H. (2020). Carnitine palmitoyltransferase 1C contributes to progressive cellular senescence. Aging, 12(8), 6733-6755. https://doi.org/10.18632/aging.103033