Mitocytosis, a migrasome-mediated mitochondrial quality-control process

Extracellular vesicles (EVs) are membranous structures containing bioactive molecules, secreted by most cells into the extracellular environment. EVs are classified by their biogenesis mechanisms into two major subtypes: ectosomes (enriched in large EVs; lEVs), budding directly from the plasma membrane, which is common in both prokaryotes and eukaryotes, and exosomes (enriched in small EVs; sEVs) generated through the multivesicular bodies via the endomembrane system, which is unique to eukaryotes. Even though recent proteomic analyses have identified key proteins associated with EV subtypes, there has been no systematic analysis, thus far, to support the general validity and utility of current EV subtype separation methods, still largely dependent on physical properties, such as vesicular size and sedimentation. Here, we classified human EV proteomic datasets into two main categories based on distinct centrifugation protocols commonly used for isolating sEV or lEV fractions. We found characteristic, evolutionarily conserved profiles of sEV and lEV proteins linked to their respective biogenetic origins. This may suggest that the evolutionary trajectory of vesicular proteins may result in a membership bias toward specific EV subtypes. Protein–protein interaction (PPI) network analysis showed that vesicular proteins formed distinct clusters with proteins in the same EV fraction, providing evidence for the existence of EV subtype-specific protein recruiters. Moreover, we identified functional modules enriched in each fraction, including multivesicular body sorting for sEV, and mitochondria cellular respiration for lEV proteins. Our analysis successfully captured novel features of EVs embedded in heterogeneous proteomics studies and suggests specific protein markers and signatures to be used as quality controllers in the isolation procedure for subtype-enriched EV fractions.

Section: Discussionsupporting

confidence: 51%

Extracellular Vesicle Proteomes Shed Light on the Evolutionary, Interactive, and Functional Divergence of Their Biogenesis Mechanisms

Lim

Yoon

Kim

et al. 2021

“…In addition, unhealthy mitochondria received by macrophages may be extruded by migrasomes, which are newly identified vesicular structures that discharge cellular contents during migration ( Ma et al, 2015 ). In an ex vivo study, BMMs exposed to mild mitochondria stress induced by carbonyl cyanide 3-chlorophenylhydrazone were observed to leave behind migrasomes containing damaged mitochondria ( Jiao et al, 2021 ), indicating that BMMs may be donor cells for mitochondrial transfers ( Jiao et al, 2021 ). Further studies are required to determine whether migrasomes containing mitochondria are received by surrounding cells as a route of mitochondrial transfer.…”

Section: Discussionmentioning

confidence: 99%

Macrophages as Emerging Key Players in Mitochondrial Transfers

Pang

Zhang

Gao

2021

Macrophages are a group of heterogeneous cells widely present throughout the body. Under the influence of their specific environments, via both contact and noncontact signals, macrophages integrate into host tissues and contribute to their development and the functions of their constituent cells. Mitochondria are essential organelles that perform intercellular transfers to regulate cell homeostasis. Our review focuses on newly discovered roles of mitochondrial transfers between macrophages and surrounding cells and summarizes emerging functions of macrophages in transmitophagy, metabolic regulation, and immune defense. We also discuss the negative influence of mitochondrial transfers on macrophages, as well as current therapies targeting mitochondria in macrophages. Regulation of macrophages through mitochondrial transfers between macrophages and their surrounding cells is a promising therapy for various diseases, including cardiovascular diseases, inflammatory diseases, obesity, and cancer.

“…In addition, the mechanism of mitochondrial quality control is being further improved. Recently, Yu et al discovered a new mechanism called mitocytosis, which is a migrasome-mediated mitochondrial quality control process, maintaining mitochondrial membrane potential and viability in neutrophils (Jiao et al, 2021). However, several questions remain.…”

Section: Discussionmentioning

confidence: 99%

The Loss of Mitochondrial Quality Control in Diabetic Kidney Disease

Dai

Chen

et al. 2021

Diabetic kidney disease (DKD) is the predominant complication of diabetes mellitus (DM) and the leading cause of chronic kidney disease and end-stage renal disease worldwide, which are major risk factors for death. The pathogenesis of DKD is very complicated, including inflammation, autophagy impairment, oxidative stress, and so on. Recently, accumulating evidence suggests that the loss of mitochondrial quality control exerts critical roles in the progression of DKD. Mitochondria are essential for eukaryotic cell viability but are extremely vulnerable to damage. The mechanisms of mitochondrial quality control act at the molecular level and the organelle level, including mitochondrial dynamics (fusion and fission), mitophagy, mitochondrial biogenesis, and mitochondrial protein quality control. In this review, we summarize current knowledge of the role of disturbances in mitochondrial quality control in the pathogenesis of DKD and provide potential insights to explore how to delay the onset and development of DKD.