Fig. 7.

Early glucose induced changes in mitochondria may lead to diabetic nephropathy: a schematic diagram with each box referring to key findings of this paper given in brackets. The early changes refer to data obtained from cultured renal cells. The late changes refer to data obtained from PBMCs from HC, DC and DN patients. The evidence supporting this schematic in the paper: hyperglycaemia leads to increased MtDNA content (Fig. 4A), altered mitochondrial morphology (Fig. 5, F–H), increased intracellular reactive oxygen species (ROS Fig. 5A), mitochondrial DNA damage (Fig. 5C), cellular damage measured as apoptosis/viability (Fig. 5B), and inflammation (Fig. 5, D and E) as early changes in cells. These changes precede and are followed by reduced OCR (basal, maximal, ATP-linked), reserve capacity and ECAR (Fig. 6, A–E). These changes may result in damaged mitochondria, blocked mitochondrial biogenesis and an energy deficit. The long term consequences of such changes could be as shown in the bottom panel. In DC patients these changes are seen as an increase in MtDNA (Fig. 1A) and normal metabolism (Fig. 2, A–E) however DN patients have decreased MtDNA (Fig. 1A) accompanied with a dysfunctional metabolic response (Fig. 2A–E) resulting in reduced BHI (Fig. 2F). There is evidence of reduced mitophagy in both DC and DN patients (Fig. 1, K and L).