Neuron-specific knockdown of Drosophila PDHB induces reduction of lifespan, deficient locomotive ability, abnormal morphology of motor neuron terminals and photoreceptor axon targeting

Journal Article · Tue May 15 04:00:00 EDT 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.02.035· OSTI ID:23082386

Dung, Vuu My ^[1]; Suong, Dang Ngoc Anh ^[1]; Okamaoto, Yuji; Hiramatsu, Yu ^[2]; Thao, Dang Thi Phuong ^[3]; Yoshida, Hideki ^[1]; Takashima, Hiroshi ^[2]; Yamaguchi, Masamitsu ^[1]

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1. Department of Applied Biology, The Center for Advanced Insect Research, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585 (Japan)
2. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima (Japan)
3. Department of Molecular and Environmental Biotechnology, Faculty of Biology and Biotechnology, University of Science, Vietnam National University – Ho Chi Minh City, Ho Chi Minh City 700000 (Viet Nam)

Highlights: • Drosophila CG11876 (dPDHB) is a homolog of human pyruvate dehydrogenase beta, PDHB. • Neuron-specific knockdown of dPDHB causes locomotive defects and reduced life span. • Neuron-specific knockdown of dPDHB causes structural defects in NMJ. • Neuron-specific knockdown of dPDHB induces mitochondrial fragmentation in brain. • Knockdown of dPDHB induces a rough eye and aberrant photoreceptor axon targeting. Pyruvate dehydrogenase complex deficiency (PDCD) is a common primary cause of defects in mitochondrial function and also can lead to peripheral neuropathy. Pyruvate dehydrogenase E1 component subunit beta (PDHB) is a subunit of pyruvate dehydrogenase E1, which is a well-known component of PDC. In Drosophila melanogaster, the CG11876 (dPDHB) gene is a homolog of human PDHB. In this study, we established a Drosophila model with neuron-specific knockdown of dPDHB to investigate its role in neuropathy pathogenesis. Knockdown of dPDHB in pan-neurons induced locomotor defects in both larval and adult stages, which were consistent with abnormal morphology of the motor neuron terminals at neuromuscular junctions and mitochondrial fragmentation in brains. Moreover, neuron-specific knockdown of dPDHB also shortened the lifespan of adult flies. In addition, flies with knockdown of dPDHB manifested a rough eye phenotype and aberrant photoreceptor axon targeting. These results with the Drosophila model suggest the involvement of PDHB in peripheral neuropathy.

• OSTI ID: 23082386
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 366; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BRAIN
DROSOPHILA
HUMAN POPULATIONS
MITOCHONDRIA
NERVE CELLS
OXIDOREDUCTASES