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2016-02-03

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cc-by (c) Gavaldà i Navarro, Aleix et al., 2016
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/116046

Changes in the expression of the human adenine nucleotide translocase isoforms condition cellular metabolic/proliferative status

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https://doi.org/10.1098/rsob.150108

Abstract

Human cells express four mitochondrial adenine nucleotide translocase (hANT) isoforms that are tissue-specific and developmentally regulated. hANT1 is mainly expressed in terminally differentiated muscle cells; hANT2 is growth-regulated and is upregulated in highly glycolytic and proliferative cells; and hANT3 is considered to be ubiquitous and non-specifically regulated. Here, we studied how the expression of hANT isoforms is regulated by proliferation and in response to metabolic stimuli, and examined the metabolic consequences of their silencing and overexpression. In HeLa and HepG2 cells, expression of hANT3 was upregulated by shifting metabolism towards oxidation or by slowed growth associated with contact inhibition or growth-factor deprivation, indicating that hANT3 expression is highly regulated. Under these conditions, changes in hANT2 mRNA expression were not observed in either HeLa or HepG2 cells, whereas in SGBS preadipocytes (which, unlike HeLa and HepG2 cells, are growth-arrest-sensitive cells), hANT2 mRNA levels decreased. Additionally, overexpression of hANT2 promoted cell growth and glycolysis, whereas silencing of hANT3 decreased cellular ATP levels, limited cell growth and induced a stress-like response. Thus, cancer cells require both hANT2 and hANT3, depending on their proliferation status: hANT2 when proliferation rates are high, and hANT3 when proliferation slows.

Subject

Adenina, Proliferació cel·lular, Expressió gènica, Glucòlisi, Mitocondris

Subject (English)

Adenine, Cell proliferation, Gene expression, Glycolysis, Mitochondria

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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GAVALDÀ I NAVARRO, Aleix, MAMPEL ASTALS, Teresa and VIÑAS I FOLCH, Octavi. Changes in the expression of the human adenine nucleotide translocase isoforms condition cellular metabolic/proliferative status. Open Biology. 2016. Vol. 6, num. 150108. ISSN 2046-2441. [consulted: 12 of August of 2026]. Available at: https://hdl.handle.net/2445/116046

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