Unc51-like-kinase 1-mediated mitophagy prevents pathological cardiac remodelling and heart failure

This editorial refers to ‘Ulk1-dependent alternative mitophagy plays a protective role during pressure overload in the heart’ by J. Nah et al.,https://doi.org/10.1093/cvr/cvac003. The quintessential response of the myocardium to increased work load is heart hypertrophy. Heart hypertrophy is an adaptive response mechanism that promotes growth of the heart muscle in attempt to normalize diastolic filling pressure.1 Cardiac hypertrophy can result from an increase in peripheral resistance, valvular defects, or cardiac injury following myocardial infarction. These changes set into motion a cascade of signalling events that promote cardiac myocyte growth. The physiological increase in cardiac wall mass off-sets the increased ventricular loading conditions and maintains cardiac function according to the Laws of Laplace, reviewed in.2,3 In general, the heart is among the most metabolically active organs in the body with a high energy demand for maintaining normal cardiac functioning, which rises exponentially in response to hypertrophic growth. For this reason, cardiac myocytes rely heavily on mitochondrial oxidative metabolism as the primary adenosine triphosphate (ATP) source and is reflected by the fact that more than 30% of the cardiac myocyte volume is comprised of mitochondria. However, with the continuous loss of functional mitochondria and consequential decline in ATP, the adaptive hypertrophic response can readily transition into pathological hypertrophy resulting in heart failure.4