Accumulating evidence has shown that dysfunctional mitochondria can be selectively removed by mitophagy. Dysregulation of mitophagy is implicated in the development of neurodegenerative disease and metabolic disorders. How individual mitochondria are recognized for removal and how this process is regulated remain poorly understood. Here we report that FUNDC1, an integral mitochondrial outer-membrane protein, is a receptor for hypoxia-induced mitophagy. FUNDC1 interacted with LC3 through its typical LC3-binding motif Y(18)xxL(21), and mutation of the LC3-interaction region impaired its interaction with LC3 and the subsequent induction of mitophagy. Knockdown of endogenous FUNDC1 significantly prevented hypoxia-induced mitophagy, which could be reversed by the expression of wild-type FUNDC1, but not LC3-interaction-deficient FUNDC1 mutants. Mechanistic studies further revealed that hypoxia induced dephosphorylation of FUNDC1 and enhanced its interaction with LC3 for selective mitophagy. Our findings thus offer insights into mitochondrial quality control in mammalian cells.

MicroRNAs (miRNAs) are a class of noncoding RNAs that regulate target gene expression at the posttranscriptional level. Here, we report that secreted miRNAs can serve as signaling molecules mediating intercellular communication. In human blood cells and cultured THP-1 cells, miR-150 was selectively packaged into microvesicles (MVs) and actively secreted. THP-1-derived MVs can enter and deliver miR-150 into human HMEC-1 cells, and elevated exogenous miR-150 effectively reduced c-Myb expression and enhanced cell migration in HMEC-1 cells. In vivo studies confirmed that intravenous injection of THP-1 MVs significantly increased the level of miR-150 in mouse blood vessels. MVs isolated from the plasma of patients with atherosclerosis contained higher levels of miR-150, and they more effectively promoted HMEC-1 cell migration than MVs from healthy donors. These results demonstrate that cells can secrete miRNAs and deliver them into recipient cells where the exogenous miRNAs can regulate target gene expression and recipient cell function.

The principal lipids in animal cell lipid droplets are cholesterol, cholesterol ester, and triglyceride, but the protein composition of this compartment is largely unknown. Here we report on the proteomic analysis of lipid droplets. Using a combination of mass spectrometry and immunoblotting, we identify nearly 40 specifically associated proteins in droplets isolated from Chinese hamster ovary K2 cells grown in normal medium. The proteins fall in to five groups: structural molecules of the droplet-like adipose differentiation-related protein; multiple enzymes involved in the synthesis, storage, utilization, and degradation of cholesterol esters and triglycerides; multiple, different Rab GTPases known to be involved in regulating membrane traffic; signaling molecules such as p50RhoGAP; and a group of proteins that do not fit any classification but include proteins often found in caveolae/rafts such as caveolin-1 and 2 and flotillin-1. The proteome of droplets isolated from cells grown in the presence of oleate is largely the same except for an increase in the amount of adipose differentiation-related protein, caveolin-1, and a protein thought to be involved in phospholipid recycling called CGI-58. Based on the protein profile, the lipid droplet appears to be a complex, metabolically active organelle that is directly involved in membrane traffic and possibly phospholipid recycling. We propose the name adiposome for this organelle.Lipid droplets are generally regarded as simple storage depots for neutral lipids in animal and plant cells. Their morphologic appearance gives the impression they are inert cellular inclusions that derive metabolic sustenance solely from their association with smooth endoplasmic reticulum, mitochondria, or peroxisomes (1). This is especially true in professional fat storing cells of plant seeds and adipose tissue where they occupy much of the cytoplasmic space.Plant and animal lipid droplets are coated with proteins that may regulate their size. Plant oleosins, a large family of structurally related proteins, form a capsule around seed lipid bodies (2). By contrast, a family of four proteins (ADRP, 1 perilipin, S3-12, and TIP47) that share a 100-amino-acid-long region of homology at the N terminus called the PAT domain are associated with the periphery of animal lipid droplets (3). ADRP, perilipin, and S3-12 are expressed highly in adipocytes. Unlike perilipin and S3-12, ADRP is expressed ubiquitously. Both the oleosins and the PAT domain proteins may function as barriers that control the lipolysis of core lipids (4). Apparently oleosins and PAT domain proteins are not strictly required for the generation and stability of a lipid droplet because these proteins are not found in yeast (Saccharomyces cerevisiae) lipid droplets (5). Instead, the predominant proteins in the lipid droplet fraction of these cells are enzymes involved in sterol and triglyceride metabolism. The localization of these enzymes to yeast lipid droplets suggests that the droplet is a metabolic organelle with a central ...

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