Sex differences and gonadal hormone regulation of brain cardiolipin, a key mitochondrial phospholipid

Estefania Acaz-Fonseca, Ana Ortiz-Rodriguez, Luis Miguel Garcia-Segura, Mariana Astiz*

*Corresponding author for this work
2 Citations (Scopus)


Cardiolipin (CL) is a phospholipid that is almost exclusively located in the inner mitochondrial membrane of eukaryotic cells. As a result of its unique structure and distribution, CL establishes non-covalent bonds with a long list of proteins involved in ATP production, mitochondria biogenesis, mitophagy and apoptosis. Thus, the amount of CL, as well as its fatty acid composition and location, strongly impacts upon mitochondrial-dependent functions and therefore the metabolic homeostasis of different tissues. The brain is particularly sensitive to mitochondrial dysfunction as a result of its high metabolic demand. Several mitochondrial related-neurodegenerative disorders, as well as physiological ageing, show altered CL metabolism. Furthermore, mice lacking enzymes involved in CL synthesis show cognitive impairments. CL content and metabolism are regulated by gonadal hormones in the developing and adult brain. In neuronal cultures, oestradiol increases CL content, whereas adult ovariectomy decreases CL content and alters CL metabolism in the hippocampal mitochondria. Transient sex differences in brain CL metabolism have been detected during development. At birth, brain CL has a higher proportion of unsaturated fatty acids in the brain of male mice than in the brain of females. In addition, the expression of enzymes involved in CL de novo and recycling synthetic pathways is higher in males. Most of these sex differences are abolished by the neonatal androgenisation of females, suggesting a role for testosterone in the generation of sex differences in brain CL. The regulation of brain CL by gonadal hormones may be linked to their homeostatic and protective actions in neural cells, as well as the manifestation of sex differences in neurodegenerative disorders.

Original languageEnglish
Article numbere12774
JournalJournal of Neuroendocrinology
Issue number1
Publication statusPublished - 01.01.2020

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


Dive into the research topics of 'Sex differences and gonadal hormone regulation of brain cardiolipin, a key mitochondrial phospholipid'. Together they form a unique fingerprint.

Cite this