Mitochondrial metabolism and hypoxic signaling in differentiated human cardiomyocyte AC16 cell line

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F25%3A00619841" target="_blank" >RIV/67985823:_____/25:00619841 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/25:10501990

Result on the web

<a href="https://doi.org/10.1152/ajpcell.00083.2025" target="_blank" >https://doi.org/10.1152/ajpcell.00083.2025</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1152/ajpcell.00083.2025" target="_blank" >10.1152/ajpcell.00083.2025</a>

Result language

angličtina

Original language name

Mitochondrial metabolism and hypoxic signaling in differentiated human cardiomyocyte AC16 cell line

Original language description

Cardiovascular diseases are associated with an altered cardiomyocyte metabolism. Because of a shortage of human heart tissue, experimental studies mostly rely on alternative approaches including animal and cell culture models. Since the use of isolated primary cardiomyocytes is limited, immortalized cardiomyocyte cell lines may represent a useful tool as they closely mimic human cardiomyocytes. This study is focused on the AC16 cell line generated from adult human ventricular cardiomyocytes. Despite an increasing number of studies employing AC16 cells, a comprehensive proteomic, bioenergetic, and oxygen-sensing characterization of proliferating vs. differentiated cells is still lacking. Here, we provide a comparison of these two stages, particularly emphasizing cell metabolism, mitochondrial function, and hypoxic signaling. Label-free quantitative mass spectrometry revealed a decrease in autophagy and cytoplasmic translation in differentiated AC16, confirming their phenotype. Cell differentiation led to global increase in mitochondrial proteins [e.g. oxidative phosphorylation (OXPHOS) proteins, TFAM, VWA8] reflected by elevated mitochondrial respiration. Fatty acid oxidation proteins were increased in differentiated cells, whereas the expression levels of proteins associated with fatty acid synthesis were unchanged and glycolytic proteins were decreased. There was a profound difference between proliferating and differentiated cells in their response to hypoxia and anoxia-reoxygenation. We conclude that AC16 differentiation leads to proteomic and metabolic shifts and altered cell response to oxygen deprivation. This underscores the requirement for proper selection of the particular differentiation state during experimental planning. NEW & NOTEWORTHY Proliferating and differentiated AC16 cell lines exhibit distinct proteomic and metabolic profiles with critical implications for experimental design. Proliferating cells predominantly utilize glycolysis and are highly sensitive to hypoxia, whereas differentiated cells display enhanced mitochondrial biogenesis, oxidative phosphorylation, and resistance to anoxia-reoxygenation. These findings provide novel insights into the metabolic adaptations during differentiation and highlight the necessity of selecting the appropriate cellular stage to ensure accurate experimental outcomes.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

American Journal of Physiology-Cell Physiology

ISSN

0363-6143

e-ISSN

1522-1563

Volume of the periodical

328

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

"C1571"-"C1585"

UT code for WoS article

001484068600007

EID of the result in the Scopus database

2-s2.0-105004224623