Mitochondrial lipidome's fatty acid profile and peroxidation index are programmed tissue-specific traits

Mitochondria are dynamic systems adapted to the different cellular demands. In this context, it is hypothesized that lipids, and particularly fatty acids, are also affected by these adaptations and supported at transcriptional level. By analyzing seven mammalian organs from rats, covering the three germ layers and belonging to the four basic types of tissue, we evaluated the differences in the lipidome's fatty acid profiles, calculated fatty acidderived parameters including susceptibility to lipid peroxidation, and estimated enzymatic activity. Then, we analyzed gene expression datasets of rat tissues to identify specific signatures supporting fatty acid profiles and extended the analysis to human datasets to evaluate shared and differential traits. Our findings demonstrate that a) mitochondrial lipotype is determined by the basic type of tissue instead of the germ layer origin; b) mitochondrial fatty acid profiles define the tissue; c) myristic acid (FA14:0) and docosapentaenoic acid n-6 (22:5n-6) act as biomarkers for global definition of the tissue mitotype; d) brain and adipose tissue mitochondria are especially resistant to lipid peroxidation; e) mitochondrial fatty acid signatures are supported at transcriptional level; and f) tissue-specific transcriptomic patterns of elongase and desaturase expression in rats are largely conserved in humans (e.g., Elovl4, Elovl7, Scd, and Fads6), although species-specific differences are observed for certain transcripts, such as Elovl2, Elovl3, and Elovl5. Our findings suggest that mitochondria share general intertissue features but also exhibit tissue-specific specializations in their lipid phenotype. We infer that the mitochondrial fatty acid composition and its derived peroxidation index may be programmed, tissue-specific traits. Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.