Role of AMPK/mTOR, mitochondria, and ROS in the pathogenesis of endometriosis

Life Sci. 2022 Oct 1:306:120805. doi: 10.1016/j.lfs.2022.120805. Epub 2022 Jul 15.

Abstract

Endometriosis is the presence of endometrial tissue outside the uterine cavity usually in the ovaries, fallopian tube, and pelvic cavity. It's a chronic enigmatic gynecological condition associated with dysmenorrhea, dyspareunia, pelvic pain, and infertility. Endometriosis lesions exist in a unique microenvironment characterized by increased concentrations of hormones, inflammation, and oxidative stress. This environment promotes cell survival through the binding of membrane receptors and subsequent cascading activation of intracellular kinases that stimulate a cellular response. In endometriosis, well-established signaling pathways, mTOR and AMPK, are altered via steroid hormones and other factors to promote cell growth, migration, and proliferation. This is accompanied by dysfunction in the mitochondria that increase energy production to sustain proliferation demands consequently leading to reactive oxygen species overproduction. This review aims to summarize the role of altered mTOR/AMPK signaling pathway, mitochondrial dysfunction, and reactive oxygen species overproduction along with providing therapeutic and diagnostic approaches. Highlighting these factors would provide a better understanding to reach a coherent theory for the pathogenesis of endometriosis.

Keywords: AMPK; Endometriosis; Inflammation; Mitochondrial dysfunction; Reactive oxygen species; mTOR.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Endometriosis* / metabolism
  • Female
  • Hormones / metabolism
  • Humans
  • Mitochondria / metabolism
  • Reactive Oxygen Species / metabolism
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Hormones
  • Reactive Oxygen Species
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases