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Review
. 2023 Oct 8;30(1):85.
doi: 10.1186/s12929-023-00979-3.

Extracellular release in the quality control of the mammalian mitochondria

Kuei-Hsiang Pan  1   2 , Hung Chang  1 , Wei Yuan Yang  3   4
Affiliations
Review

Extracellular release in the quality control of the mammalian mitochondria

Kuei-Hsiang Pan et al. J Biomed Sci. .

Abstract

Mammalian cells release a wealth of materials to their surroundings. Emerging data suggest these materials can even be mitochondria with perturbed morphology and aberrant function. These dysfunctional mitochondria are removed by migrating cells through membrane shedding. Neuronal cells, cardiomyocytes, and adipocytes send dysfunctional mitochondria into the extracellular space for nearby cells to degrade. Various studies also indicate that there is an interplay between intracellular mitochondrial degradation pathways and mitochondrial release in handling dysfunctional mitochondria. These observations, in aggregate, suggest that extracellular release plays a role in quality-controlling mammalian mitochondria. Future studies will help delineate the various types of molecular machinery mammalian cells use to release dysfunctional mitochondria. Through the studies, we will better understand how mammalian cells choose between intracellular degradation and extracellular release for the quality control of mitochondria.

Keywords: Autophagy; Extracellular vesicles; Mitochondria; Mitophagy; Organelle quality control.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Organelle Extracellular Release. a. Melanosome extracellular release: melanosomes, derived from multivesicular bodies (MVBs), are transported to the tip of melanocytes’ dendrites and released. The released melanosomes are subsequently taken up by neighboring keratinocytes. Yellow: Endoplasmic reticulum (ER); Red: Golgi apparatus b. Lipid droplet extracellular release in mammary epithelial cells: lipid droplets, originating from the endoplasmic reticulum (ER), bud off and fuse with the plasma membrane, forming milk fat globules (MFGs). Figure created with BioRender.com
Fig. 2
Fig. 2
Mitochondria Extracellular Release as a Quality Control Mechanism. a. Damaged mitochondria are selectively transported to migrasomes through retraction fibers and released. b. (1) Neurons are able to deliver damaged mitochondria to adjacent astrocytes for their degradation. (2) Meanwhile, astrocytes can deliver functional mitochondria back to neurons in order to compensate for malfunctioning mitochondria. (3) When neurons suffer from undesirable conditions, Schwann cells can release mtDNA and cytochrome C as warnings to inform neurons of potential danger and degeneration. c. Mitochondria quality control in cardiomyocytes occurs through two pathways. One, cardiomyocytes can release damaged mitochondria to cardiac macrophage through exophers for degradation. Two, the damaged mitochondria can also be degraded by mitophagy. Figure created with BioRender.com
Fig. 3
Fig. 3
Mitochondrial Quality Control Pathways. Cells utilize a number of strategies to maintain mitochondria quality. a. Mitochondrial dynamics. A damaged segment of mitochondria splits off from healthy mitochondria. b. Lysosomal degradation of damaged mitochondria. Damaged mitochondrial fragments can be engulfed into phagophores, and delivered into lysosomes for degradation. This process is termed mitophagy. On the other hand, malfunctioning portion of mitochondria can be packed into small vesicles which bud off from mitochondria called mitochondria derived vesicles (MDVs). MDVs can be delivered to lysosomes and degraded. c. Mitochondrial extracellular release. (1) Damaged mitochondria can be removed through several extracellular release processes as shown in Fig. 2. (2) The lack of ATG8-PE on autophagosomes results in autophagosome-mediated mitochondrial release into the extracellular space. Figure created with BioRender.com
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