acyl-CoA dehydrogenase family member 9
The ACAD9 gene provides instructions for making an enzyme that is found in mitochondria, the energy-producing structures inside cells. The ACAD9 enzyme is critical in helping assemble a group of proteins known as complex I. Complex I is one of several complexes that carry out a multistep process called oxidative phosphorylation, through which cells derive much of their energy.
The ACAD9 enzyme also plays a role in fatty acid oxidation, a multistep process that occurs within mitochondria to break down (metabolize) fats and convert them into energy. The ACAD9 enzyme helps metabolize two fats called palmitate and oleate, which belong to a certain group of fats called long-chain fatty acids. Fatty acids are a major source of energy for the heart and muscles. During periods without food (fasting), fatty acids are also an important energy source for the liver and other tissues.
At least 30 ACAD9 gene mutations have been found to cause ACAD9 deficiency. This condition varies in severity and can cause muscle weakness (myopathy), heart problems, intellectual disability, and other signs and symptoms. Most ACAD9 gene mutations change single protein building blocks (amino acids) in the ACAD9 enzyme. Some mutations disrupt only complex I assembly. Decreased complex I formation can impair oxidative phosphorylation and reduce the amount of energy available in the cell. Other mutations affect the ACAD9 enzyme's structure or stability and likely disrupt both complex I assembly and long-chain fatty acid oxidation. A reduction in both of these energy production processes tends to be associated with the most severe signs and symptoms of ACAD9 deficiency.
Although the exact mechanism that causes the signs and symptoms of ACAD9 deficiency is unclear, it is likely that cells that are less able to produce energy die off, particularly cells in the brain, skeletal muscle, and other tissues and organs that require a lot of energy. The loss of cells in these tissues is thought to lead to myopathy and other features of ACAD9 deficiency.
Genetics Home Reference provides information about mitochondrial complex I deficiency.
- acyl-CoA dehydrogenase family member 9, mitochondrial
- acyl-Coenzyme A dehydrogenase family, member 9
- Biochemistry (fifth edition, 2002): Certain Fatty Acids Require Additional Steps for Degradation
- Biochemistry (fifth edition, 2002): The Utilization of Fatty Acids as Fuel Requires Three Stages of Processing
- The Cell: A Molecular Approach (second edition, 2000): The Mechanism of Oxidative Phosphorylation
- Washington University, St Louis: Neuromuscular Disease Center