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. 2019 May 24:10:595.
doi: 10.3389/fphys.2019.00595. eCollection 2019.

LRPPRC: A Multifunctional Protein Involved in Energy Metabolism and Human Disease

Jie Cui  1   2 , Li Wang  1   2 , Xiaoyue Ren  1   2 , Yamin Zhang  1   2 , Hongyi Zhang  2   3
Affiliations

LRPPRC: A Multifunctional Protein Involved in Energy Metabolism and Human Disease

Jie Cui et al. Front Physiol. .

Abstract

The pentatricopeptide repeat (PPR) family plays a major role in RNA stability, regulation, processing, splicing, translation, and editing. Leucine-rich PPR-motif-containing protein (LRPPRC), a member of the PPR family, is a known gene mutation that causes Leigh syndrome French-Canadian. Recently, growing evidence has pointed out that LRPPRC dysregulation is related to various diseases ranging from tumors to viral infections. This review presents available published data on the LRPPRC protein function and its role in tumors and other diseases. As a multi-functional protein, LRPPRC regulates a myriad of biological processes, including energy metabolism and maturation and the export of nuclear mRNA. Overexpression of LRPPRC has been observed in various human tumors and is associated with poor prognosis. Downregulation of LRPPRC inhibits growth and invasion, induces apoptosis, and overcomes drug resistance in tumor cells. In addition, LRPPRC plays a potential role in Parkinson's disease, neurofibromatosis 1, viral infections, and venous thromboembolism. Further investigating these new functions of LRPPRC should provide novel opportunities for a better understanding of its pathological role in diseases from tumors to viral infections and as a potential biomarker and molecular target for disease treatment.

Keywords: LRPPRC; LSFC; cancer; energy metabolism; mitochondria.

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Figures

Figure 1
Figure 1
Domain structure of LRPPRC. Phosphorylation sites are located in the 1026–1138 amino acid sequence of the C-terminal domain.
Figure 2
Figure 2
Regulatory pathways of LRPPRC. LRPPRC plays key roles in regulating OXPHOS activity, mitophagy and maturation and export of nuclear mRNA. MTORC1 activation increases the expression of LRPPRC. Energy stress increases SIRT3 activity, which promotes deacetylation of LRPPRC for increased OXPHOS activity.
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