Mechanisms of Mitochondrial Quality Control: From Classical Pathways to Mitochondrial Aggregates

Mitochondria rely on a complex network of quality control mechanisms to preserve their structure and function under stress. This review summarizes well-established pathways, including mitochondrial biogenesis, cytosolic quality control of protein import, mitochondrial dynamics, mitophagy, and the mitochondrial Unfolded Protein Response (mtUPR), alongside emerging or less characterized processes such as mitochondria-derived vesicles (MDVs), nucleoid-phagy, mitochondrial transfer, and mitoptosis. We then discuss the hypothesis that, when these pathways are overwhelmed, irreversibly damaged mitochondrial components are sequestered into intramitochondrial aggregates that may give rise to lipofuscin-like material. We examine the evidence for and against a protective role of these aggregates, their possible pathological consequences, and the context-dependent benefits and limitations of therapeutically targeting mitochondrial quality control.