Iron loss triggers mitophagy through induction of mitochondrial ferritin
| Autor: | Sohji Nishina, John J. Lemasters, Fumio Kishi, Izumi Yanatori, Kyo Sasaki, Keisuke Hino, Atsushi Tanaka, Yuichi Hara |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Carcinoma
Hepatocellular Iron Mitochondrion Biochemistry Mitochondrial Proteins 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Coactivator Mitophagy Genetics Gene silencing Animals News & Views Molecular Biology 030304 developmental biology 0303 health sciences Chemistry Autophagy Liver Neoplasms MITOCHONDRIAL FERRITIN Articles Cell biology Nuclear receptor Ferritins Deferiprone 030217 neurology & neurosurgery |
| Zdroj: | EMBO Rep |
| ISSN: | 1469-3178 |
| Popis: | Mitochondrial quality is controlled by the selective removal of damaged mitochondria through mitophagy. Mitophagy impairment is associated with aging and many pathological conditions. An iron loss induced by iron chelator triggers mitophagy by a yet unknown mechanism. This type of mitophagy may have therapeutic potential, since iron chelators are clinically used. Here, we aimed to clarify the mechanisms by which iron loss induces mitophagy. Deferiprone, an iron chelator, treatment resulted in the increased expression of mitochondrial ferritin (FTMT) and the localization of FTMT precursor on the mitochondrial outer membrane. Specific protein 1 and its regulator hypoxia‐inducible factor 1α were necessary for deferiprone‐induced increase in FTMT. FTMT specifically interacted with nuclear receptor coactivator 4, an autophagic cargo receptor. Deferiprone‐induced mitophagy occurred selectively for depolarized mitochondria. Additionally, deferiprone suppressed the development of hepatocellular carcinoma (HCC) in mice by inducing mitophagy. Silencing FTMT abrogated deferiprone‐induced mitophagy and suppression of HCC. These results demonstrate the mechanisms by which iron loss induces mitophagy and provide a rationale for targeting mitophagic activation as a therapeutic strategy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text