ATP5A (ATP synthase F1 subunit alpha) is a key component of the mitochondrial ATP synthase complex, also known as Complex V or F1F0 ATP synthase, which is responsible for ATP production through oxidative phosphorylation. This enzyme complex consists of two major domains: the F1 catalytic core and the Fo membrane proton channel. ATP5A encodes the alpha subunit of the F1 domain, which is essential for ATP synthesis. It is ubiquitously expressed in various tissues, including the heart, kidney, and nervous system. In addition to its role in energy metabolism, ATP5A has been implicated in cancer progression. For example, it interacts with MTA1 (metastasis-associated protein 1) to drive mitochondrial metabolic reprogramming and enhance oxidative phosphorylation, thereby promoting liver metastasis in colorectal cancer. Overexpression of ATP5A has also been observed in metastatic lung adenocarcinomas, highlighting its potential role in tumor development. Defects in ATP5A1 have been linked to severe mitochondrial disorders, such as neonatal mitochondrial encephalopathy. Given its critical function in ATP synthesis and involvement in disease processes, ATP5A1 is an important target for understanding mitochondrial dysfunction and developing therapeutic strategies.
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