Iron derived from autophagy-mediated ferritin degradation induces cardiomyocyte death and heart failure in mice

© 2021, Ito et al..

Heart failure is a major public health problem, and abnormal iron metabolism is common in patients with heart failure. Although iron is necessary for metabolic homeostasis, it induces a programmed necrosis. Iron release from ferritin storage is through nuclear receptor coactivator 4 (NCOA4)-mediated autophagic degradation, known as ferritinophagy. However, the role of ferritinophagy in the stressed heart remains unclear. Deletion of Ncoa4 in mouse hearts reduced left ventricular chamber size and improved cardiac function along with the attenuation of the upregulation of ferritinophagy-mediated ferritin degradation 4 weeks after pressure overload. Free ferrous iron overload and increased lipid peroxidation were suppressed in NCOA4-deficient hearts. A potent inhibitor of lipid peroxidation, ferrostatin-1, significantly mitigated the development of pressure overload-induced dilated cardiomyopathy in wild-type mice. Thus, the activation of ferritinophagy results in the development of heart failure, whereas inhibition of this process protects the heart against hemodynamic stress.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

eLife - 10(2021) vom: 02. Feb.

Sprache:

Englisch

Beteiligte Personen:

Ito, Jumpei [VerfasserIn]
Omiya, Shigemiki [VerfasserIn]
Rusu, Mara-Camelia [VerfasserIn]
Ueda, Hiromichi [VerfasserIn]
Murakawa, Tomokazu [VerfasserIn]
Tanada, Yohei [VerfasserIn]
Abe, Hajime [VerfasserIn]
Nakahara, Kazuki [VerfasserIn]
Asahi, Michio [VerfasserIn]
Taneike, Manabu [VerfasserIn]
Nishida, Kazuhiko [VerfasserIn]
Shah, Ajay M [VerfasserIn]
Otsu, Kinya [VerfasserIn]

Links:

Volltext

Themen:

9007-73-2
Autophagy
Biochemistry
Chemical biology
Cyclohexylamines
E1UOL152H7
Ferritin
Ferritins
Ferrostatin-1
Heart failure
Iron
Journal Article
Medicine
Mouse
NcoA4 protein, mouse
Necrosis
Nuclear Receptor Coactivators
Phenylenediamines
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 02.02.2022

Date Revised 26.02.2024

published: Electronic

Citation Status MEDLINE

doi:

10.7554/eLife.62174

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM320872009