Human mitochondrial mRNA turnover, one of the key processes governing the gene expression inside the organelle, remains so far the unsolved puzzle. Neither the possible pathway nor the enzymes involved have been identified. Mitochondrial mRNA molecules lack the 5’-cap structure, but the transcripts are constitutively polyadenylated and therefore possess stable 3’- poly(A) extensions. However the stabilising effect of polyadenylation observed in the eukaryotic cytosol has not been shown in the mammalian mitochondria and the existence of a protective poly(A)-binding protein is uncertain. To date, both in silico and biochemical studies of the mammalian mitochondrial proteome have failed to reveal any obvious candidates for the ribonucleases involved in the degradation of the mitochondrial transcripts. We present the results of our search for the proteins involved in the mt-mRNA turnover. A range of biochemical methods including 2D gel electrophoresis and zymography has been applied to analyse the ribonucleolytic activities from the mitochondrial subfractions. We have revealed a limited number of ribonuclease activities and have subsequently commenced mitochondrial protein fractionation in harness with RNA degradation assays to identify and characterise the candidates for the mRNA-metabolising enzymes. These studies attempt to shed some light on the molecular mechanism governing mRNA metabolism and the role of polyadenylation in the human mitochondria.