Loss of mitochondria long-chain fatty acid oxidation impairs skeletal muscle contractility by disrupting myofibril structure and calcium homeostasis.

ABSTRACT:

Objective

Abnormal lipid metabolism in mammalian tissues can be highly deleterious, leading to organ failure. Carnitine Palmitoyltransferase 2 (CPT2) deficiency is an inherited metabolic disorder affecting the liver, heart, and skeletal muscle due to impaired mitochondrial oxidation of long-chain fatty acids (mLCFAO) for energy production.

Methods

However, the basis of tissue damage in mLCFAO disorders is not fully understood. Mice lacking CPT2 in skeletal muscle (Cpt2^Sk-/-) were generated to investigate the nexus between mFAO deficiency and myopathy.

Results

Compared to controls, ex-vivo contractile force was reduced by 70% in Cpt2^Sk-/- oxidative soleus muscle despite the preserved capacity to couple ATP synthesis to mitochondrial respiration on

SUBMITTER: Pereyra AS 

PROVIDER: S-EPMC11408158 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature