NUCLEAR RESPONSES TO DEPLETION OF MITOCHONDRIAL-DNA IN HUMAN-CELLS

The derivation of human cell lines devoid of mitochondrial (mt) DNA (r ho O) provides an opportunity to study nuclear responses to a chronic impairment of mitochondrial oxidative phosphorylation. Expression of s everal nuclear genes is induced in human rho O cells, including those encoding integral proteins of the mitochondrial inner membrane, interm ediate filaments, and ribosomes. In contrast to conditions in which mi tochondrial respiration is altered acutely, expression of heat shock p roteins and immediate early genes is not induced. Mitochondria from rh o O cells maintain a transmembrane electrochemical potential and are d istributed within the cytoplasm of these cells in a manner indistingui shable from that of wild-type cells. We conclude that a chronic defici ency of mitochondrial oxidative phosphorylation produced by eliminatio n of mtDNA is associated with a different pattern of gene induction th an that provoked by other acute or subacute conditions that impair mit ochondrial respiration or create energy demands in excess of mitochond rial respiratory capacity.