AMPK regulates Bcl2-L-13-mediated mitophagy induction for cardioprotection

The accumulation of damaged mitochondria in the heart is associated with heart failure. Mitophagy is an autophagic degradation system that specifically targets damaged mitochondria. We have reported previously that Bcl2-like protein 13 (Bcl2-L-13) mediates mitophagy and mitochondrial fission in mammalian cells. However, the in vivo function of Bcl2-L-13 remains unclear. Here, we demonstrate that Bcl2-L-13-deficient mice and knockin mice, in which the phosphorylation site (Ser272) on Bcl2-L-13 was changed to Ala, showed left ventricular dysfunction in response to pressure overload. Attenuation of mitochondrial fission and mitophagy led to impairment of ATP production in these mouse hearts. In addition, we identified AMPKα2 as the kinase responsible for the phosphorylation of Bcl2-L-13 at Ser272. These results indicate that Bcl2-L-13 and its phosphorylation play an important role in maintaining cardiac function. Furthermore, the amplitude of stress-stimulated mitophagic activity could be modulated by AMPKα2.

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Publication Details

Journal
Cell Reports
Published
2024-11-23
DOI
https://doi.org/10.1016/j.celrep.2024.115001
Citations
11
Primary Topic
Autophagy in Disease and Therapy
Type
article
Field-Weighted Citation Impact
4.25

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article

AMPK regulates Bcl2-L-13-mediated mitophagy induction for cardioprotection

Manabu Taneike, Ryuta Sugihara, Tomokazu Murakawa, Shigemiki Omiya et al.
11 citations
Cell Reports
Autophagy in Disease and Therapy
4.25
article

AMPK regulates Bcl2-L-13-mediated mitophagy induction for cardioprotection

Manabu Taneike, Ryuta Sugihara, Tomokazu Murakawa, Shigemiki Omiya, Javier Moncayo, Osamu Yamaguchi, Hiroki Nishida, Yasushi Sakata, Kentaro Mine, Chiaki Nakanishi, Kazuhiko Nishida, Jumpei Ito, Mara-Camelia Rusu, Roland A. Fleck, Ajay M. Shah, Kinya Otsu, M. Zhang
article en
11 citations

Abstract

The accumulation of damaged mitochondria in the heart is associated with heart failure. Mitophagy is an autophagic degradation system that specifically targets damaged mitochondria. We have reported previously that Bcl2-like protein 13 (Bcl2-L-13) mediates mitophagy and mitochondrial fission in mammalian cells. However, the in vivo function of Bcl2-L-13 remains unclear. Here, we demonstrate that Bcl2-L-13-deficient mice and knockin mice, in which the phosphorylation site (Ser272) on Bcl2-L-13 was changed to Ala, showed left ventricular dysfunction in response to pressure overload. Attenuation of mitochondrial fission and mitophagy led to impairment of ATP production in these mouse hearts. In addition, we identified AMPKα2 as the kinase responsible for the phosphorylation of Bcl2-L-13 at Ser272. These results indicate that Bcl2-L-13 and its phosphorylation play an important role in maintaining cardiac function. Furthermore, the amplitude of stress-stimulated mitophagic activity could be modulated by AMPKα2.

Cell ReportsVol. 43(12)
King's College London (GB), British Heart Foundation (GB), National Cerebral and Cardiovascular Center (JP), Ehime University (JP), The University of Osaka (JP)
British Heart Foundation, Fondation Leducq, European Research Council, Japan Society for the Promotion of Science
Openalex Percentile: Top 5%
Autophagy in Disease and Therapy
4.25
DOIOpen Access PDFOpenAlex
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