1. Figure 3 Physiological regulation of autophagy in the heart
Figure 3 | Physiological regulation of autophagy in the heart. Cardiomyocyte energy status regulates autophagy via metabolic signalling. A substrate deficit (for example, during nutrient deprivation or hypoxia) leads to low ATP levels, which stimulate 5′-AMP-activated kinase (AMPK) activity. AMPK activates autophagy via stimulating serine/threonine-protein kinase ULK1 and phosphatidylinositol 3-kinase class III (PI3K(III)) and inhibiting suppressors of autophagy, such as mechanistic target of rapamycin complex 1 (mTORC1) and c-Jun N-terminal kinase (JNK), which promotes the interaction of apoptosis regulator Bcl-2 and Beclin 1. Therefore, Beclin 1 is prevented from moving to the PI3K(III) complex for autophagy. Growth or cell survival stimuli activate insulin or insulin-like growth factor (IGF) signalling in cardiomyocytes, leading to activation of the insulin receptor substrate 1 (IRS1)/PI3K(I)/Akt pathway. Activation of GTP-binding protein Rheb results in inhibition of autophagy via activation of autophagy suppressors (primarily mTORC1) and inhibition of transcription factors forkhead box protein (FOX) O1/3 and transcription factor EB (TFEB).
Delbridge, L. M. D. et al. (2017) Myocardial stress and autophagy: mechanisms and potential therapies
Nat. Rev. Cardiol. doi: /nrcardio