ACOT7

ACOT7 Full Name

acyl-CoA thioesterase 7

ACOT7 Introduction

Acyl-CoA Thioesterase 7 (ACOT7), also known as mitochondrial acyl-CoA thioesterase or MTE-1, is a member of the acyl-CoA thioesterase (ACOT) family, specialized in regulating lipid metabolism within mitochondria—the primary organelle for fatty acid oxidation and energy production. Unlike ACOT11 and other cytosolic ACOT family members, ACOT7 is exclusively localized to the mitochondrial matrix, where it catalyzes the hydrolysis of short-chain and medium-chain acyl-CoA esters to free fatty acids and coenzyme A (CoA). This reaction is critical for maintaining mitochondrial lipid homeostasis, preventing the accumulation of toxic acyl-CoA intermediates that can impair mitochondrial function. ACOT7 is widely expressed across mammalian tissues, with highest expression in organs dependent on mitochondrial energy metabolism, including the heart, skeletal muscle, liver, and brain. Today, ACOT7 is recognized not only as a key regulator of mitochondrial lipid metabolism but also as a critical mediator of mitochondrial function and energy homeostasis, with profound implications for metabolic disorders, mitochondrial diseases, and neurodegeneration research.

Figure 1.The structure of ACOT7.

Expression Pattern and Regulatory Mechanisms of ACOT7
ACOT7 exhibits a tissue-specific expression pattern closely linked to mitochondrial density and energy demand, distinguishing it from the more ubiquitous ACOT11. It is highly expressed in tissues with high mitochondrial content, such as cardiac muscle (where mitochondria provide energy for continuous contraction), skeletal muscle (supporting exercise-induced energy production), and the liver (facilitating fatty acid oxidation during fasting). Lower expression levels are found in tissues with minimal mitochondrial activity, such as epithelial tissues. The expression of ACOT7 is tightly regulated by mitochondrial stress responses and metabolic signaling pathways. Key regulators include peroxisome proliferator-activated receptor alpha (PPARα), which upregulates ACOT7 expression in response to fatty acid excess and fasting, promoting mitochondrial fatty acid oxidation. Additionally, ACOT7 expression is modulated by AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis that activates ACOT7 during energy deprivation to optimize mitochondrial function. Post-translational modifications, including phosphorylation and acetylation, fine-tune ACOT7's enzymatic activity and mitochondrial localization. Aberrant regulation of ACOT7, driven by genetic variation or mitochondrial dysfunction, disrupts mitochondrial lipid balance and contributes to disease development.

Biological Functions of ACOT7
ACOT7's core biological function is the hydrolysis of short-chain and medium-chain acyl-CoA esters within the mitochondrial matrix, a reaction critical for mitochondrial health and energy metabolism. By breaking down these acyl-CoA intermediates, ACOT7 releases free fatty acids that can be fully oxidized via the tricarboxylic acid (TCA) cycle and oxidative phosphorylation to generate ATP. This process prevents the buildup of acyl-CoA esters, which can inhibit mitochondrial enzymes and disrupt membrane integrity. ACOT7 also plays a key role in regulating mitochondrial CoA availability, ensuring that CoA is recycled and available for essential metabolic reactions, including fatty acid synthesis and oxidation. In cardiac and skeletal muscle, ACOT7 supports sustained energy production during periods of increased demand (e.g., exercise). In the liver, it facilitates fatty acid oxidation during fasting, helping to maintain blood glucose levels. Beyond energy metabolism, ACOT7 is involved in mitochondrial stress responses—its activity increases in response to oxidative stress and mitochondrial damage, helping to restore mitochondrial homeostasis. It also modulates cellular apoptosis, as impaired mitochondrial function (linked to ACOT7 dysregulation) can trigger apoptotic pathways.

Alternate Names for ACOT7

ACOT7; acyl-CoA thioesterase 7; cytosolic acyl coenzyme A thioester hydrolase; ACH1; ACT; BACH; brain acyl CoA hydrolase; CTE II; hBACH; LACH1