Abstract
Traumatic brain injury (TBI) contributes to death, and disability worldwide more than any other traumatic insult and damage to cellular components including mitochondria leads to the impairment of cellular functions and brain function. In neurons, mitophagy, autophagy-mediated degradation of damaged mitochondria, is a key process in cellular quality control including mitochondrial homeostasis and energy supply and plays a fundamental role in neuronal survival and health. Conversely, defective mitophagy leads to the accumulation of damaged mitochondria and cellular dysfunction, contributing to inflammation, oxidative stress, and neuronal cell death. Therefore, an extensive characterization of mitophagy-related protective mechanisms, taking into account the complex mechanisms by which each molecular player is connected to the others, may provide a rationale for the development of new therapeutic strategies in TBI patients. Here, we discuss the contribution of defective mitophagy in TBI, and the underlying molecular mechanisms of mitophagy in inflammation, oxidative stress, and neuronal cell death highlight novel therapeutics based on newly discovered mitophagy-inducing strategies.
Highlights
Mitochondria are organelles coated by bilayer membranes, mitochondrial inner membrane (IMM), and mitochondrial outer membrane (OMM), which are the main places for cellular respiration and energy production [1]
The other mechanism of mitophagy induced by stress, such as ROS and hypoxia, is regulated by mitochondrial receptors such as BCL2/adenovirus E1B kDa interacting protein 3 (BNIP3), BNIP3L/NIX, FUN14 domain containing 1 (FUNDC1), and Cardiolipin (CL) which directly bind with LC3 through the conserved LC3 interacting region (LIR) motif
Ren et al found that the expression of PINK1 was significantly induced by traumatic brain injury (TBI), and RvD1 treatment successfully downregulated it [29]. These results suggested that downregulation of PINK1/Parkin-mediated mitophagy might play an important role in recovery after
Summary
Mitochondria are organelles coated by bilayer membranes, mitochondrial inner membrane (IMM), and mitochondrial outer membrane (OMM), which are the main places for cellular respiration and energy production [1]. The brain consumes approximately 20% of the total body energy even though it accounts for only 2% of the body weight [4]. This huge energy consumption depends on the utilization of glucose and the maintenance of mitochondrial function [5]. Mitophagy is a crucial process of eliminating old or damaged mitochondria for the maintenance of the integrity of the mitochondrial pool for cellular homeostasis, which impacts various physiological and pathological courses in the brain. This review is aimed at describing the research progress of mitophagy including the molecular pathways that govern mitophagy and the role of mitophagy in different aspects of TBI and other brain diseases, to develop potential therapeutics for clinical treatment (Figure 1)
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