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Review
. 2019 Jan 1:1702:96-104.
doi: 10.1016/j.brainres.2018.06.010. Epub 2018 Jun 9.

LRRK2 and mitochondria: Recent advances and current views

Alpana Singh  1 , Lianteng Zhi  1 , Hui Zhang  2
Affiliations
Review

LRRK2 and mitochondria: Recent advances and current views

Alpana Singh et al. Brain Res. .

Abstract

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene account for most common causes of familial and sporadic Parkinson's disease (PD) and are one of the strongest genetic risk factors in sporadic PD. Pathways implicated in LRRK2-dependent neurodegeneration include cytoskeletal dynamics, vesicular trafficking, autophagy, mitochondria, and calcium homeostasis. However, the exact molecular mechanisms still need to be elucidated. Both genetic and environmental causes of PD have highlighted the importance of mitochondrial dysfunction in the pathogenesis of PD. Mitochondrial impairment has been observed in fibroblasts and iPSC-derived neural cells from PD patients with LRRK2 mutations, and LRRK2 has been shown to localize to mitochondria and to regulate its function. In this review we discuss recent discoveries relating to LRRK2 mutations and mitochondrial dysfunction.

Keywords: LRRK2; Mitochondrial dynamics; Mitochondrial dysfunction; Mitophagy; Parkinson’s disease; Trafficking.

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Figures

Fig 1:
Fig 1:. Diagram showing pathways and molecules affecting mitochondrial function.
Abbreviations: Bcl-2: B-cell lymphoma 2; DRP1: dynamin like protein; 4E-BP1: eukaryotic translation initiation factor 4E-binding protein 1; MCU: mitochondrial calcium uniporter; OPA1: optic atrophy 1: PRDX3: peroxiredoxin 3
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