Nuclear responses to depletion of mitochondrial dna in human
cells.
Li, Kang, P. Darrell Neufer, and R. Sanders Williams.
Departments of Internal Medicine and Biochemistry, The University
of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235
-8573
APStracts 2:0206C, 1995.
The derivation of human cell lines devoid of mtDNA (r0) provides an
opportunity to study nuclear responses to a chronic impairment of
mitochondrial oxidative phosphorylation. Expression of several
nuclear genes is induced in human r0 cells, including those encoding
integral proteins of the mitochondrial inner membrane, intermediate
filaments, and ribosomes. In contrast to conditions in which
mitochondrial respiration is altered acutely, expression of heat
shock proteins and immediate early genes is not induced. Mitochondria
from r0 cells maintain a transmembrane electrochemical potential and
are distributed within the cytoplasm of these cells in a manner
indistiguishable from wild type cells. We conclude that a chronic
deficiency of mitochondrial oxidative phosphorylation produced by
elimination of mtDNA is associated with a different pattern of gene
induction than that provoked by other acute or subacute conditions
that impair mitochondrial respiration or create energy demands in
excess of mitochondrial respiratory capacity.
Received 30 November 1994; accepted in final form 11 May 1995.
APS Manuscript Number C701-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.