Autophagy‐independent mitochondrial quality control: Mechanisms and disease associations

Abstract Maintaining a healthy and functional mitochondrial network is crucial for cell survival and function. Protein misfolding and dysfunction are particularly prevalent in them due to physiological adaptations and stress conditions. For mitochondria to function properly, multiple quality control systems have evolved to ensure that there are enough mitochondria to meet cells’ needs, damaged mitochondrial proteins or mitochondrial parts can be eliminated using these pathways. Several mechanisms control mitochondrial quality, including protein, organelle, and cellular levels. As the extensive study of canonical mitochondrial quality‐mitophagy, this paper reviews the processes and mechanisms of mitochondrial quality control independent of autophagy, including mitochondrial protein and DNA degradation, mitochondria‐derived vesicles and mitochondria‐derived compartments, mitochondrial secretion, tunneling nanotubes, mitocytosis, and mitolysosome exocytosis. Understanding these novel quality control pathways may provide insights into mitochondrial homeostasis and for developing targeted treatments for diseases where these systems fail.