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.
Highlights
Ageing manifests itself in the progressive decline of biological functions, reducing the capability of an organism to respond to internal and external stress [1]
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
Brain and muscle mitochondria each have characteristic compositions, and the lipid composition of each is strongly affected by increased age (Fig. 1)
Summary
Ageing manifests itself in the progressive decline of biological functions, reducing the capability of an organism to respond to internal and external stress [1]. Mass spectrometry based lipidomics has revealed the complex lipid composition ranging from organelles and cells to tissues and whole organisms [6,7]. Whilst the lipid composition of the mitochondrion has been investigated [8,9,10] little is known about the changes to the whole mitochondrial lipidome in different tissue types with ageing [11]. Mitochondria are highly specialised organelles with a complex structure consisting of two membranes. Lipids are distributed differently between the inner mitochondrial membrane and outer mitochondrial membrane. The outer mitochondrial membrane is fluid and contains higher levels of cholesterol and phosphatedylinositol. The inner mitochondrial membrane is highly folded, enriched in phosphatidylethanolamines and contains cardiolipin, a component synthesised and restricted to this membrane layer [12]. Mitochondria are characterised by a high, phospphatidylethanolamine and phosphatidylcholine content and low levels of sterols and sphingolipids [13]
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