Drp1 and Mitochondrial Autophagy Lend a Helping Hand in Adaptation to Pressure Overload
The heart undergoes hypertrophy in response to pressure overload, a response generally considered to be an adaptive mechanism to reduce increased wall stress. When the stress is too great, or other molecular changes are elicited, hypertrophy can decompensate leading to development of heart failure. Macroautophagy (hereafter referred to as autophagy) has been implicated in this process. Autophagy is an intracellular system whereby cytoplasmic components and damaged organelles are sequestered in double-membrane vesicles called autophagosomes and delivered to lysosomes for degradation. Nutrient starvation or cellular stress rapidly induce autophagy, providing amino acids and fatty acids to synthesize proteins and to generate ATP, while also eliminating damaged mitochondria.1-4 Damaged mitochondria are the major source of reactive oxygen species (ROS) contributing to apoptotic and necrotic cell death thus preservation of mitochondrial integrity is critical for cell survival. Mitochondrial quality control can be achieved through autophagy, mitochondria-selective autophagy (mitophagy), fission/fusion and mitochondrial biogenesis, processes that are in many ways interrelated.5 There are, however, contradictory published observations regarding the timing or direction of changes in general autophagy and its functional significance in the cardiac response to pressure overload remains controversial.2-4,6,7 Moreover, whether the regulation of mitochondrial quality control by autophagy is beneficial or deleterious in the development of pressure overload-induced hypertrophy or its transition to heart failure has not been extensively studied.
- Received February 22, 2016.
- Accepted February 24, 2016.