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September 28, 2026Journal of the Endocrine SocietyOpen Access

Angiotensin II and cAMP signaling increase mitochondrial biogenesis, respiration, and ATP production in adrenocortical cells.

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Why the study?

The hormonal regulation of genes governing mitochondrial function in human adrenocortical cells remains poorly understood.

Population

Human adrenocortical H295R cell line

Comparison

Angiotensin II, 8Br-cAMP, and CCCP treatments vs control

Design

Preclinical experimental study

Key result

Angiotensin II and cAMP signaling increased mitochondrial biogenesis, basal and maximum respiration, and ATP production in human adrenocortical H295R cells.

Authors

MBMatías A. BellunoFAFabrizio G. AronaKHKatia E. Helfenberger

Discussion

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Overview

No immediate clinical implications for adrenal disorders; leaves open whether mitochondrial modulation alters steroidogenesis in vivo.

Key Points

  • To determine whether angiotensin II and cAMP/PKA signaling regulate genes controlling mitochondrial biogenesis, redox balance, and respiration in human adrenocortical cells.
  • Treated human adrenocortical H295R cells with angiotensin II, the cell-permeant cAMP analogue 8Br-cAMP, and the mitochondrial uncoupler CCCP.
  • Assessed gene and protein expression using real-time qPCR and Western blot, and evaluated mitochondrial membrane potential via MitoTracker red staining.
  • Quantified oxygen consumption rates (basal respiration, maximal respiration, ATP production, and proton leak) and quantified mitochondrial DNA content.
  • Angiotensin II and 8Br-cAMP modulated NRF-1, Nrf2, UCP2, and ANT1 expression and induced mitochondrial membrane hyperpolarization.
  • Angiotensin II stimulation induced a time-dependent increase in TFAM expression that correlated with increased mitochondrial DNA content.
  • Angiotensin II significantly elevated basal respiration, maximal respiration, ATP turnover, and proton leak, while CCCP-induced depolarization prompted retrograde upregulation of nuclear mitochondrial genes.

Structured PICO

P
Population
Human adrenocortical H295R cell line
I
Intervention
Angiotensin II (Ang II), 8Br-cAMP (a permeant analogue of cAMP), and CCCP (uncoupler)
O
Outcome
Expression of key regulatory factors involved in mitochondrial biogenesis and redox status (NRF-1, Nrf2, UCP2, ANT1, TFAM), mitochondrial DNA content, mitochondrial membrane polarization, and oxygen consumption rate (OCR)surrogate

Angiotensin II and cAMP signaling directly modulate the mitochondrial genetic program in human adrenocortical cells, optimizing the bioenergetic platform required for efficient steroidogenic function.

Cite This Study

Belluno et al. (2026) studied this question. Angiotensin II and 8Br-cAMP was evaluated on Expression of key regulatory factors involved in mitochondrial biogenesis and redox status. Angiotensin II and cAMP signaling increased mitochondrial biogenesis, basal and maximum respiration, and ATP production in human adrenocortical H295R cells.

synapsesocial.com/papers/6ab9b5da7822ec8fc3d9117ehttps://doi.org/10.1210/jendso/bvag218
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Also Consider

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