Cytoplasmic genetics of mammalian cells: Conditional sensitivity to mitochondrial inhibitors and isolation of new mutant phenotypes

We report here that glucose, as a carbon source, and pyruvate are required for the phenotypic expression of cytoplasmically transmitted chlor-amphenicol-resistance (CAP-R) mutations, recovery of CAP-R mutants, and continuous growth in the presence of oligomycin or antimycin. We assume that glucose supplies additional energy when mitochondrial respiration is diminished and that pyruvate provides intermediates when the Krebs cycle is inhibited. Thus, the requirement for pyruvate is fully satisfied by an exogenous source of purines, and partially by -ketoglutarate or a pyrimidine source. Based upon these findings, we have obtained two types of mutations affecting mitochondrial function—oligomycin resistance and pyruvate-independent expression of chloramphenicol resistance. Both are cytoplasmically transmitted and provide new markers for a genetic analysis of mitochondrial biogenesis.This paper is dedicated to the memory of Boris Ephrussi, whose pioneering work in gene expression, mitochondrial biogenesis, and somatic cell genetics has been a continuing inspiration and guide to both of us. Ruth Sager further expresses her indebtedness for the intellectual companionship and moral support that Boris provided so generously in the dark dawn of cytoplasmic inheritance.