Details

Autor(en) / Beteiligte

• Zhang, Xiaomin
• Sun, Congcong
• Wan, Jinliang
• Zhang, Xiaoxue
• Jia, Yanhan
• Zhou, Chao

Titel

Compartmentalized activities of HMGCS1 control cervical cancer radiosensitivity

Ist Teil von

• Cellular signalling, 2023-01, Vol.101, p.110507-110507, Article 110507

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• The underlying mechanisms by which cellular metabolism affects cervical cancer cell radiosensitivity remain poorly understood. Here, we found that loss of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 (HMGCS1), a key enzyme catalyzing the conversion of acetoacetyl-CoA to HMG-CoA in the cholesterol biosynthesis pathway, sensitizes the cervical cancer cells to radiation. We observed a compartmentalized cellular distribution of HMGCS1 in nuclei, cytosol, and mitochondria of cervical cancer cells and found that cytosolic HMGCS1 and mitochondrial HMGCS1 contribute together to the regulation of radiosensitivity. Mechanistically, we show that cytosolic HMGCS1 regulates radiosensitivity via manipulating the cholesterol metabolism, while mitochondrial HMGCS1 controls mitochondrial gene expression, thereby sustaining the mitochondrial function of cervical cancer cells. Together, our study identifies HMGCS1 as a novel regulator of radiosensitivty in cervical cancer cells, providing a molecular link between altered cholesterol metabolism, mitochondrial respiration, and radiosensitivity. Thus, targeting HMGCS1 may improve the therapeutic outcome of cervical cancer radiotherapy. •HMGCS1 resides in the nuclei, cytosol, and mitochondria of cervical cancer cells.•Cytosolic HMGCS1 controls radiosensitivity via regulation of cholesterol metabolism.•Mitochondrial HMGCS1 governs radiosensitivity via modulating mitochondrial function.•Targeting mitochondrial function radiosensitizes cervical cancer cells.