The β-subunit of ATP synthase is involved in cellular uptake and resecretion of apoA-I but does not control apoA-I-induced lipid efflux in adipocytes

Abstract

Cellular uptake and resecretion of apoA-I (apoA-I recycling) could be an important factor in determining the circulating plasma levels of apoA-I and/or HDL. Using a novel method to study protein recycling, we have recently demonstrated recycling of apoA-I by adipocytes and suggested that this is a receptor mediated process independent of ABCA1 function. In the present study, it is shown that apoA-I recycling by adipocytes can be blocked by a monoclonal antibody against the β-subunit of ATP synthase, a protein that had been previously identified as an apoA-I receptor. Investigation of the cellular recycling of two other proteins, an apolipoprotein and a small globular protein, showed that recycling of apoA-I is a selective process. The present study also shows that blocking apoA-I recycling has no effect on the rate of apoA-I-induced cholesterol or phospholipid efflux. It is concluded that cellular recycling of apoA-I is a selective process that involves the ectopically expressed β-subunit of ATP synthase. The physiological function of apoA-I recycling remains to be elucidated. However, this study shows that the process of apoA-I uptake and resecretion is not required for apoA-I lipidation.

The β-Chain of Cell Surface F 0 F 1 ATPase Modulates ApoA-I and HDL Transcytosis Through Aortic Endothelial Cells

“…In contrast, at 37°C the cell association and the transport of both apoA-I and HDL were diminished by the stream receptor. 10 In line with observations and conclusions of Howard and colleagues made in experiments with adipocytes, 33 our findings suggest that in addition to mature HDL also lipid-free apoA-I can be internalized by this pathway. However, based on our previously reported findings that initially lipid-free apoA-I is lipidated by ABCA1 for subsequent ABCA1-independent internalization and transport, we assume that a nascent lipidated apoA-I particle rather than lipid-free apoA-I is the substrate for ␤-ATPase triggered endocytosis.…”

“…In this regard it is interesting to note that ␤-ATPase was previously shown to modulate the internalization and resecretion of apoA-I by adipocytes without affecting phospholipid and cholesterol efflux. 33 The interaction of ABCG1, SR-BI, and the ␤-ATPase-ADP-P2Y 12 -axis is even more elusive. Figure 6 summarizes our current model of transendothelial transport of apoA-I and HDL: By lipidating apoA-I, ABCA1 generates a particle that is then processed by ABCA1-independent mechanisms for transendothelial transport.…”

Retinoic acid-induced differentiation increases the rate of oxygen consumption and enhances the spare respiratory capacity of mitochondria in SH-SY5Y cells

“…We analyzed the expression level of nuclear-encoded mitochondrial complex I subunit NDUFB8 (Davis et al, 2010), complex II subunit A (Gleason et al, 2011), complex III subunit core 2 (Suthammarak et al, 2010), and ATP synthase beta subunit (Howard et al, 2011), as well as MT-encoded complex IV subunit II (Pang et al, 2011) using specific antibodies (Fig. 6C).…”

PI3Kβ Plays a Key Role in Apolipoprotein A-I-Induced Endothelial Cell Proliferation Through Activation of the Ecto-F1-ATPase/P2Y1 Receptors

“…All of the three P2Y receptors that are preferentially activated by ADP (P2Y 1 , P2Y 12 and P2Y 13 ) have been found to be coupled to ecto-F 1 -ATPase activity and display different functions depending on the cell type [32]. For instance, in hepatocytes the apoA-I/ecto-F 1 -ATPase/P2Y 13 axis activates an intracellular RhoA/ROCKI signaling pathway that stimulates HDL uptake and appears to have atheroprotective properties by promoting reverse cholesterol transport [21-24, 30, 44, 45], and in adipocytes HDL-apoA-I, ecto-F 1 -ATPase and P2Y signaling are all involved in lipid metabolism [46-50]. In endothelial cells, apoA-I/ecto-F 1 -ATPase has been previously shown to stimulate HDL transcytosis via activation of P2Y 12 ADP receptors [20].…”