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

Area of Science:

• Cardiology
• Cell Biology
• Mitochondrial Biology

Background:

• Accumulation of damaged mitochondria contributes to heart failure.
• Mitophagy is a key cellular process for removing damaged mitochondria.
• Bcl2-like protein 13 (Bcl2-L-13) is known to mediate mitophagy and mitochondrial fission in vitro.

Purpose of the Study:

• To investigate the in vivo function of Bcl2-L-13 in cardiac health.
• To elucidate the role of Bcl2-L-13 phosphorylation in cardiac function under stress.
• To identify the kinase responsible for Bcl2-L-13 phosphorylation.

Main Methods:

• Generation and analysis of Bcl2-L-13-deficient and knockin mice (Ser272Ala).
• Assessment of cardiac function, mitochondrial fission, and mitophagy under pressure overload.
• Identification of the kinase responsible for Bcl2-L-13 phosphorylation using biochemical assays.

Main Results:

• Bcl2-L-13 deficiency and impaired phosphorylation led to left ventricular dysfunction.
• Mitochondrial fission and mitophagy were attenuated, impairing ATP production in affected hearts.
• AMPKα2 was identified as the kinase phosphorylating Bcl2-L-13 at Ser272.

Conclusions:

• Bcl2-L-13 and its phosphorylation by AMPKα2 are critical for maintaining cardiac function.
• This pathway is essential for mitochondrial quality control and energy production in the heart.
• AMPKα2 activity modulates stress-induced mitophagy, offering a potential therapeutic target.