Nuclear-mitochondrial crosstalk: On the role of the nuclear receptor liver receptor homolog-1 (NR5A2) in the regulation of mitochondrial metabolism, cell survival, and cancer

IUBMB Life. 2021 Mar;73(3):592-610. doi: 10.1002/iub.2386. Epub 2020 Sep 15.

Abstract

Liver receptor homolog-1 (LRH-1, NR5A2) is an orphan nuclear receptor with widespread activities in the regulation of development, stemness, metabolism, steroidogenesis, and proliferation. Many of the LRH-1-regulated processes target the mitochondria and associated activities. While under physiological conditions, a balanced LRH-1 expression and regulation contribute to the maintenance of a physiological equilibrium, deregulation of LRH-1 has been associated with inflammation and cancer. In this review, we discuss the role and mechanism(s) of how LRH-1 regulates metabolic processes, cell survival, and cancer in a nuclear-mitochondrial crosstalk, and evaluate its potential as a pharmacological target.

Keywords: apoptosis; cancer; metabolism; mitochondria; nuclear receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Nucleus / metabolism
  • Cell Survival
  • Endoplasmic Reticulum Stress
  • Humans
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Molecular Targeted Therapy / methods
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Oncogenes
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • NR5A2 protein, human
  • Nr5a2 protein, mouse
  • Receptors, Cytoplasmic and Nuclear