Trafficking pathway between plasma membrane and mitochondria via clathrin-mediated endocytosis

Endocytosis is a basic cellular process that describes a form of active transport across the plasma membrane into the cell.The endocytic pathway consists of distinct membrane compartments;internalized molecules are delivered to early endosomes,and some of them are recycled back to the surface,whereas other molecules are sent to late endosomes and lysosomes for degradation.However,little is known about how mitochondria are involved in the endocytic pathway.Here,we report that FM dyes, membrane-impermeant fluorescent lipid probes,can traffic to mitochondria directly from the plasma membrane by clathrinmediated endocytosis.FM dye entry into mitochondria uses microtubule-dependent active transport,but the mechanism is different from the classical endocytic pathway.Hence,this study reveals a previously unrealized lipid trafficking pathway from the plasma membrane to mitochondria.

Transcriptome Analysis of Schwann Cells at Various Stages of Myelination Implicates Chromatin Regulator Sin3A in Control of Myelination Identity

Enhancing remyelination after injury is of utmost importance for optimizing the recovery of nerve function.While the formation of myelin by Schwann cells(SCs)is critical for the function of the peripheral nervous system,the temporal dynamics and regulatory mechanisms that control the progress of the s lineage through myelination require further elucidation.Here,using in vitro co-culture models,gene expression profiling of laser capture-microdissected SCs at various stages of myelination,and multilevel bioinformatic analysis,we demonstrated that SCs exhibit three distinct transcriptional characteristics duringmyelination:the immature,promyelinating,and myelinating states.We showed that suppressor interacting 3a(Sin3A)and 16 other transcription factors and chromatin regulators play important roles in the progress of myelination.Sin3A knockdown in the sciatic nerve or specifically in SCs reduced or delayed the myelination of regenerating axons in a rat crushed sciatic nerve model,while overexpression of Sin3A greatly promoted the remyelination of axons.Further,in vitro experiments revealed that Sin3A silencing inhibited SC migration and differentiation at the promyelination stage and promoted SC proliferation at the immature stage.In addition,SC differentiation and maturation may be regulated by the Sin3A/histone deacetylase2(HDAC2)complex functionally cooperating with Sox10,as demonstrated by rescue assays.Together,these results complement the recent genome and proteome analyses of SCs during peripheral nerve myelin formation.The results also reveal a key role of Sin3A-dependent chromatin organization in promoting myelinogenic programs and SC differentiation to control peripheral myelination and repair.These findings may inform new treatments for enhancing remyelination and nerveregeneration.