A MITOCHONDRIAL PORIN CDNA PREDICTS THE EXISTENCE OF MULTIPLE HUMAN PORINS

Pores formed in the outer membrane of mitochondria by mitochondrial po rin make it permeable to water-soluble metabolites smaller than approx imately 5 kDa. We have isolated a full-length cDNA encoding a human po rin. This probe detects a single approximately 1.5-kilobase mRNA speci es on Northern blots, but multiple hybridizing bands on genomic Southe rn blots. The open reading frame predicts a 38.1-kDa protein with a pl of 6.59 that is homologous but not identical to a previously reported protein sequence of a 31-kDa porin isolated from human lymphocytes (p orin 31HL). The most striking difference between the two porins is tha t the sequence predicted by the cDNA is longer than the 31HL porin by 27 amino acids at the amino terminus and 38 amino acids at the carboxy l terminus. The porin cDNA directs the in vitro translation of two pro tein species of approximately 32 and approximately 36 kDa, which appea r to result from alternate usage of AUG initiation codons. The 32-kDa protein is the predominant species imported into both rat and yeast mi tochondria in vitro. Taken together, these results suggest that multip le porin proteins can be expressed in humans. Additionally, a porin co nsensus protein sequence has been identified that is conserved in euka ryotic organisms as diverse as yeast and man.