Mouse mitochondrial lipid composition is defined by age in brain and muscle

Abstract

Functionality of the lipid rich mitochondrial organelle declines with increased age. Recent advances in lipidomic technologies allowed us to perform a global characterisation of lipid composition in two different tissue types and age ranges. Ultra-high performance liquid chromatography coupled with high resolution mass spectrometry was used to establish and compare mitochondrial lipidomes of brain and skeletal muscle from young (4-11 weeks old) and middle age (78 weeks old) healthy mice. In middle age the brain mitochondria had reduced levels of fatty acids, particularly polyunsaturated fatty acids, while skeletal muscle mitochondria had a decreased abundance of phosphatidylethanolamine, but a pronounced increase of triglyceride levels. Reduced levels of phosphatidylethanolamines are known to decrease mitochondrial membrane fluidity and are connected with accelerated ageing. In mitochondria from skeletal muscle we propose that increased age causes a metabolic shift in the conversion of diacylglycerol so that triglycerides predominate compared with phosphatidylethanolamines. This is the first time mitochondrial lipid content in normal healthy mammalian ageing brain and muscle has been catalogued in such detail across all lipid classes. We identify distinct mitochondrial lipid signatures that change with age, revealing tissue-specific lipid pathways as possible targets to ameliorate ageing-related mitochondrial decline.

Profile of cardiac lipid metabolism in STZ-induced diabetic mice

“…Phospholipids are important biomembrane components and signaling molecules [ 38 , 39 ]. A reduction in phospholipids results in mitochondrial abnormalities [ 40 – 42 ] and cardiac dysfunction [ 43 , 44 ]; therefore, the downregulation in phospholipids in the diabetic heart could also contribute to mitochondrial cristate fusion, reduced ATP production and cardiac dysfunction. Moreover, the sphingolipid metabolic pathway was constructed in the diabetic heart.…”

Linking Lipid Metabolism to Chromatin Regulation in Aging

“…Intriguingly, changes in lipid profile during aging are tissue specific. Mitochondrial lipids of old mouse brains show a decrease in PUFAs, a change normally associated with longevity [37]. In contrast, mitochondrial lipids of old mouse muscles exhibit increased triglycerides and decreased PEs [37] (Table 1), changes generally associated with aging [37].…”

“…Mitochondrial lipids of old mouse brains show a decrease in PUFAs, a change normally associated with longevity [37]. In contrast, mitochondrial lipids of old mouse muscles exhibit increased triglycerides and decreased PEs [37] (Table 1), changes generally associated with aging [37]. These differential changes in organelle lipid profiles in various tissues during aging could reflect diverse tissue-specific functions and energy requirements or compensatory protective mechanisms.…”

Low plasma lysophosphatidylcholines are associated with impaired mitochondrial oxidative capacity in adults in the Baltimore Longitudinal Study of Aging

“…LPC can be hydrolyzed to LPA by autotaxin, a secreted glycoprotein that is widely expressed in tissues (Lyu et al, ; Perrakis & Moolenaar, ) (Figure ). The membranes of both mitochondria and endoplasmic reticulum contain LPC (Pollard, Ortori, Stöger, Barrett, & Chakrabarti, ; Tsalouhidou et al, ; Veyrat‐Durebex et al, ). LPA can also be formed from the acylation of glycerol‐3‐phosphate on the outer mitochondrial membrane.…”