ミトコンドリア品質管理に関する分子薬理学的研究

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ミトコンドリア品質管理に関する分子薬理学的研究

著者佐藤岳哉

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2012$July$4th$ $

Figure 14-8 (part 1 of 2) Molecular Biology of the Cell (© Garland Science 2008) _{Figure 14-10 Molecular Biology of the Cell (© Garland Science 2008)}

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Baker BM, and Haynes CM.

Trend Biochem. Sci. 36: 254-261, 2011

! • ROS $ • $ • • • • • Common Diseases

Joseph A., et al. Exp. Diab. Res 2012, DOI: 10.1155/2012/642038 !

Mitochondrial biogenesis and Quality Control $ $ ＤＮＡ $ $ $ $ Fusion Fission Mitophagy SIRT PGC1 PGC1 AMPK Michel S. et al. J. Cell. Physiol. 227: 2297-2310, 2012.

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QC Michel S. et al. J. Cell. Physiol. 227: 2297-2310, 2012.

 AIDS  AIDS   HIV  AZT HIV  HIV HAART

HAART

HIV

NRTI: PI+NRTI/NNRTI

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AZT-metabolites"

Evoke mitochondrial biochemical dysfunction, "

leading to develop a lethal cardiac myopathy "

Formation of AZT-active

metabolite, and Pros and

Cons of AZT-metabolites

Inhibit reverse-transcription " reaction of HIV-genome"

AZTTP" AZTMP (so called)"

AZT! TK AZTMP! Tmpk AZTDP! NDK AZTTP!

Brundiers!R!et!al.!J.#Biol.#Chem.!274,!35289=35292,!1999.!

Human!thymidylate!kinase!(Tmpk)!

Induce!the!caspase=3! acIvaIon.!! Sato!T!et!al.!Mol.#Ther.#15,!962=970!(2007).##

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Schon EA., et al. Trend Mol. Med. 16 (2010), 268-276.

ND1 CO1

Ratio of mitochondrial DNA to genomic DNA is not affected by AZT

Cold Spring Harb. Perspect Biol. 3: a007559, 2011.

Baker MJ., et al. Opa1 Mfn1 Mfn2 Drp1 HtrA2 . Exp Gerontol. 45: 503-511, 2010.

Weber TA and Reichert AS.