
Mitochondrial cholesterol is maintained within a narrow range to regulate steroid and oxysterol synthesis and to ensure mitochondrial function. Mitochondria acquire cholesterol through several pathways from different cellular pools. Here we have characterized mitochondrial import of endosomal cholesterol using Chinese hamster ovary cells expressing a CYP11A1 fusion protein that converts cholesterol to pregnenolone at the mitochondrial inner membrane. RNA interference-mediated depletion of the voltage-dependent anion channel 1 in the mitochondrial outer membrane or of Niemann-Pick Type C2 (NPC2) in the endosome lumen decreased arrival of cholesterol at the mitochondrial inner membrane. Expression of NPC2 mutants unable to transfer cholesterol to NPC1 still restored mitochondrial cholesterol import in NPC2-depleted cells. Transport assays in semi-permeabilized cells showed nonvesicular cholesterol trafficking directly from endosomes to mitochondria that did not require cytosolic transport proteins but that was reduced in the absence of NPC2. Our findings indicate that NPC2 delivers cholesterol to the perimeter membrane of late endosomes, where it becomes available for transport to mitochondria without requiring NPC1.
NPC1-interaction domain, Vesicular Transport Proteins, QD415-436, CHO Cells, Endosomes, Endoplasmic Reticulum, Biochemistry, Niemann-Pick C1 Protein, Cricetinae, Animals, Humans, Glycoproteins, pregnenolone, Membrane Glycoproteins, Voltage-Dependent Anion Channel 1, Intracellular Signaling Peptides and Proteins, Biological Transport, MLN64, Mitochondria, VDAC1, Cholesterol, Chinese hamster ovary cells, Mitochondrial Membranes, semi-permeabilized cells, Carrier Proteins
NPC1-interaction domain, Vesicular Transport Proteins, QD415-436, CHO Cells, Endosomes, Endoplasmic Reticulum, Biochemistry, Niemann-Pick C1 Protein, Cricetinae, Animals, Humans, Glycoproteins, pregnenolone, Membrane Glycoproteins, Voltage-Dependent Anion Channel 1, Intracellular Signaling Peptides and Proteins, Biological Transport, MLN64, Mitochondria, VDAC1, Cholesterol, Chinese hamster ovary cells, Mitochondrial Membranes, semi-permeabilized cells, Carrier Proteins
| selected citations These citations are derived from selected sources. This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 51 | |
| popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 10% | |
| influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 10% | |
| impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 10% |
