LRRK2 impairs PINK1/Parkin-dependent mitophagy via its kinase activity: pathologic insights into Parkinson's disease.

Mutations of LRRK2, encoding leucine-rich repeat kinase 2 (LRRK2), are the leading cause of autosomal dominant Parkinson's disease (PD). The most frequent of these mutations, G2019S substitution, increases kinase activity, but it remains unclear how it causes PD. Recent studies suggest that LRRK2 modulates mitochondrial homeostasis.

The uptake of lipoprotein-borne phylloquinone (vitamin K1) by osteoblasts and osteoblast-like cells: role of heparan sulfate proteoglycans and apolipoprotein E.

Vitamin K is essential for the gamma-carboxylation of Gla-containing bone proteins such as osteocalcin and a suboptimal vitamin K status has been linked to osteoporosis but nothing is known of how the lipoprotein-borne vitamin accesses the bone matrix. We have studied the mechanism of transport of lipoproteins labeled with [3H]-phylloquinone (vitamin K1 [K1]) into osteoblasts using both tumor-derived cell lines and normal osteoblast-rich cell populations. We also investigated the effect of heparin in this model since long-term heparin treatment causes osteopenia and the anticoagulant is known to impair normal lipoprotein metabolism.