Multivesicular bodies (MVBs) are endosome organelles that are gradually attracting research attention. Initially, MVBs were considered as important components of the endosomal-lysosomal degradation pathway. In recent years, with an increase in extracellular vesicle (EV) research, the biogenesis, fate, and pathological effects of MVBs have been increasingly studied. However, the mechanisms by which MVBs are sorted to the lysosome and plasma membrane remain unclear. In addition, whether the trafficking of MVBs can determine whether exosomes are released from cells, the factors are involved in cargo loading and regulating the fate of MVBs, and the roles that MVBs play in the development of disease are unknown. Consequently, this review focuses on the mechanism of MVB biogenesis, intraluminal vesicle formation, sorting of different cargoes, and regulation of their fate. We also discuss the mechanisms of emerging amphisome-dependent secretion and degradation. In addition, we highlight the contributions of MVBs to the heterogeneity of EVs, and their important roles in cancer. Thus, we attempt to unravel the various functions of MVBs in the cell and their multiple roles in tumor progression.
12 May 2025 in Clinical and Translational Medicine
Mitochondria‐derived vesicles (MDVs) participate in early cellular defence mechanisms initiated in response to mitochondrial damage. They maintain mitochondrial quality control (MQC) by clearing damaged mitochondrial components, thereby ensuring the normal functioning of cellular processes. This process is crucial for cell survival and health, as mitochondria are the energy factories of cells, and their damage can cause cellular dysfunction and even death. Recent studies have shown that MDVs not only maintain mitochondrial health but also have a significant impact on tumour progression. MDVs selectively encapsulate and transport damaged mitochondrial proteins under oxidative stress and reduce the adverse effects of mitochondrial damage on cells, which may promote the survival and proliferation of tumour cells. Furthermore, it has been indicated that after cells experience mild stress, the number of MDVs significantly increases within 2–6 h, whereas mitophagy, a process of clearing damaged mitochondria, occurs 12–24 h later. This suggests that MDVs play a critical role in the early stress response of cells. Moreover, MDVs also have a significant role in intercellular communication, specifically in the tumour microenvironment. They can carry and transmit various bioactive molecules, such as proteins, nucleic acids, and lipids, which regulate tumour cell's growth, invasion, and metastasis. This intercellular communication may facilitate tumour spread and metastasis, making MDVs a potential therapeutic target. Advances in MDV research have identified novel biomarkers, clarified regulatory mechanisms, and provided evidence for clinical use. These breakthroughs pave the way for novel MDV‐targeted therapies, offering improved treatment alternatives for cancer patients. Further research can identify MDVs' role in tumour development and elucidate future cancer treatment horizons.