The study found that the rule of mitochondrial "black hole" phagocytosis or not

Liu Xingguo, a researcher at the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, found that the mitochondrial black hole phagocytosis rule, proposed a new mitochondrial quality control strategy based on the organelle topology. Related research was published online in Autophagy on June 25th under the topic "Topology-dependent mitochondrial quality control under starvation conditions".

According to reports, mitochondria, as the name implies, appear linear or granular, and are highly dynamic organelles. Mitochondrial autophagy plays a crucial role in development, stress and pathology. How mitochondria are recognized is mainly reported at the molecular level of PINK1/PARKIN and receptor mediated, however, its multi-level selection process and mechanism have been Not sure.

In the previous study, Liu Xingguo et al identified two basic models of mitochondrial fusion. In addition to complete fusion, a new fusion method "kiss-and-run" was discovered: two mitochondria are close together, and the soluble matter is exchanged and separated, leaving their original shape unchanged. Under pathological conditions, Liu Xingguo et al further found that hypoxia/reoxygenation caused mitochondria to exhibit a special mitochondrial ring shape, donut, and calculated its 3D energy control. However, the function of the mitochondrial donut topology is currently unclear.

Selective clearance of mitochondria by autophagy is a key strategy for a variety of physiological processes, including development, cell fate determination, and stress response. Mitochondrial autophagy is mainly regulated by receptor-mediated pathways such as PINK1/PARKIN and FUNDC1, BNIP3L, resulting in impaired or unwanted mitochondria recognized by autophagosomes, phagocytosis, and then autophagosomes fused to lysosomes to degrade mitochondria. However, the multi-layered mechanism of mitochondrial autophagy, especially the basic principles of the selection process, remains ambiguous.

The study found that under serum starvation stress conditions, mitochondria undergo a topological change that transforms into expanded and donut mitochondria. Expanded mitochondria lose mitochondrial membrane potential and recruit PINK1/PARKIN to promote autophagy degradation; while donut mitochondria maintain mitochondrial membrane potential against mitochondrial autophagy. Both mitochondrial morphology of swell and donut mitochondria are associated with mitochondrial permeability transition pore (mPTP) or potassium ion channel opening, but to varying degrees. Interestingly, even with chemical drugs that depolarize mitochondria, donut mitochondria are still resistant to autophagy, although it still recruits PINK1/PARKIN, but prevents the recruitment of autophagy receptors CALCOCO2/NDP52 and OPTN.

This study reveals a new rule for the selective control of mitochondrial mass and quantity based on mitochondrial morphological structure, which may play an important role in physiology, pathology, and development. It is worth mentioning that the control factor of mitochondrial volume-ion channel is multi-faceted: short-term opening of mitochondrial permeability transition pore can regulate epigenetics, long-term openness can be apoptosis, and can also be regulated by mitochondrial morphological structure The fate of selective degradation.

In response to his research, Liu Xingguo vividly pointed out that: looking up to the universe, the macro-scale black hole can swallow all the matter; overlooking the cell's prosperity, the tiny-scale mitochondrial "black hole" can resist being swallowed. In the small room of the cell, the autophagosome is like a child rogue in the head of the Xitou, and eats food, picky eaters and not eat mitochondrial doughnuts.

Related paper information: https://doi.org/10.1080/15548627.2019.1634944