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Yuriy Kirichok 博士は、従来適用が困難であった生体膜にパッチクランプ法を成功させ、顕著な業績を挙げている新進気鋭の研究者です。この度GCOE「生体シグナルを基盤とする統合生命学」のリトリートに参加するために来日され、東大においてご講演を頂く機会を得ました。皆様のご来聴をお待ち申し上げております。

Yuriy Kirichok 博士 (Ph.D.)
Assistant Professor&s_comma; Department of Physiology&s_comma; University of
California&s_comma; San Francisco

Mitochondrial Uncoupling Protein of Brown Fat: Electrophysiologist’s Perspective

平成23年3月7日(月) 15:00~16:00

医学部教育研究棟13階 第5セミナー室

Uncoupling proteins (UCP1- UCP5) are integral transport proteins of
the inner mitochondrial membrane (IMM) that increase its electrical
conductance and thus dissipate the mitochondrial electrochemical
proton gradient. UCPs uncouple mitochondrial respiration from ATP
synthesis and make mitochondria to produce heat rather than ATP. UCPs
contribute to thermogenesis and reduce fat depositions&s_comma; but have also
been implicated in attenuating reactive oxygen species production by
mitochondria to protect the cell against oxidative damage and ageing.
In spite of their physiological significance&s_comma; the mechanism by which
UCPs increase conductance of the IMM remain elusive due to the lack of
direct methods to measure their activity. To resolve this problem&s_comma; we
applied the patch-clamp technique to the whole IMM of mitochondria
from the brown adipose tissue to identify and characterize currents
produced by the family’s founding member&s_comma; UCP1. In our experiments&s_comma;
both the cytoplasmic and matrix faces of the IMM were exposed to
solutions that did not contain any ions normally permeable through ion
channels or transporters&s_comma; except for H+ and OH-. Under these
conditions&s_comma; we identified a current that demonstrated all signature
properties of UCP1: it was strongly potentiated by micromolar
concentrations of unsaturated fatty acids&s_comma; inhibited by removing
endogenous membrane fatty acids with bovine serum albumin&s_comma; and blocked
by micromolar concentrations of purine nucleotides. The current was
absent in the IMM of COS-7 cells&s_comma; in agreement with the fact that
UCP1 is specifically expressed in the brown adipose tissue. Finally&s_comma;
the current disappeared in UCP1 knockout mice. In this presentation&s_comma; I
will discuss the dependence of UCP1 current on the membrane potential&s_comma;
matrix and cytosolic pH&s_comma; as well as on the nature of the fatty
compounds activating the current. The ultimate goal of this work is to
elucidate the molecular mechanism employed by UCP1 and other UCPs to
uncouple the mitochondrial oxidative phosphorylation in various

Lishko PV&s_comma; Botchkina IL&s_comma; Kirichok Y. Progesterone activates the
principal Ca2+ channel of human sperm. (2011) Nature&s_comma; in press.
Lishko PV and Kirichok Y. The role of Hv1 and CatSper channels in
sperm activation. (2010) J. Physiol. 588: 4667-4672
Lishko PV&s_comma; Botchkina IL&s_comma; Fedorenko A&s_comma; Kirichok Y. Acid extrusion from
human spermatozoa is mediated by flagellar voltage-gated proton
channel. (2010) Cell 140; 327-337

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