Mitochondria in depression: The dysfunction of mitochondrial energy metabolism and quality control systems

CNS Neurosci Ther. 2024 Feb;30(2):e14576. doi: 10.1111/cns.14576.

Abstract

Background: Depression is the most disabling neuropsychiatric disorder, causing difficulties in daily life activities and social interactions. The exact mechanisms of depression remain largely unclear. However, some studies have shown that mitochondrial dysfunction would play a crucial role in the occurrence and development of depression.

Aims: To summarize the known knowledge about the role of mitochondrial dysfunction in the pathogenesis of depression.

Methods: We review the recent literature, including 105 articles, to summarize the mitochondrial energy metabolism and quality control systems in the occurrence and development of depression. Some antidepressants which may exert their effects by improving mitochondrial function are also discussed.

Results: Impaired brain energy metabolism and (or) damaged mitochondrial quality control systems have been reported not only in depression patients but in animal models of depression. Although the classical antidepressants have not been specially designed to target mitochondria, the evidence suggests that many antidepressants may exert their effects by improving mitochondrial function.

Conclusions: This brief review focuses on the findings that implicate mitochondrial dysfunction and the quality control systems as important etiological factors in the context of depressive disorders. It will help us to understand the various concepts of mitochondrial dysfunction in the pathogenesis of depression, and to explore novel and more targeted therapeutic approaches for depression.

Keywords: depression; energy metabolism; mitochondria; mitochondrial quality control system.

Publication types

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

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Depression* / drug therapy
  • Energy Metabolism
  • Humans
  • Mitochondria / metabolism
  • Mitochondrial Diseases*

Substances

  • Antidepressive Agents