Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Dysregulation of the pathways that preserve mitochondrial integrity hallmarks many human diseases including diabetes, neurodegeration, aging and cancer. The mitochondrial citrate transporter gene, SLC25A1 or CIC, maps on chromosome 22q11.21, a region amplified in some tumors and deleted in developmental disorders known as velo-cardio-facial- and DiGeorge syndromes. We report here that in tumor cells CIC maintains mitochondrial integrity and bioenergetics, protects from mitochondrial damage and circumvents mitochondrial depletion via autophagy, hence promoting proliferation. CIC levels are increased in human cancers and its inhibition has anti-tumor activity, albeit with no toxicity on adult normal tissues. The knock-down of the CIC gene in zebrafish leads to mitochondria depletion and to proliferation defects that recapitulate features of human velo-cardio-facial syndrome, a phenotype rescued by blocking autophagy. Our findings reveal that CIC maintains mitochondrial homeostasis in metabolically active, high proliferating tissues and imply that this protein is a therapeutic target in cancer and likely, in other human diseases.

Original publication

DOI

10.18632/oncotarget.714

Type

Journal article

Journal

Oncotarget

Publication Date

10/2012

Volume

3

Pages

1220 - 1235

Keywords

Adenosine Triphosphate, Animals, Autophagy, Blotting, Western, Breast Neoplasms, Cell Proliferation, Female, Fluorescent Antibody Technique, Homeostasis, Humans, Immunoenzyme Techniques, Mice, Mice, Inbred BALB C, Mice, Nude, Mitochondria, RNA, Messenger, Reactive Oxygen Species, Real-Time Polymerase Chain Reaction, Repressor Proteins, Zebrafish