Mitochondrial function in rat renal cortex in response to proteinuria and iron

Area of Science:

• Nephrology
• Mitochondrial Biology
• Cellular Injury

Background:

• Proximal tubular cell dysfunction in chronic glomerular disease (CGD) is partly attributed to transferrin-iron reabsorption and subsequent peroxidative injury.
• Altered mitochondrial function is investigated as a potential contributor to tubular cell injury in CGD.

Purpose of the Study:

• To examine renal cortical mitochondrial respiratory function in rats with adriamycin nephrosis, a model of CGD.
• To investigate the relationship between mitochondrial iron accumulation and altered respiratory function in tubular cells.

Main Methods:

• Assessed mitochondrial respiratory function (state 4, state 3, uncoupled respiration) in rats with adriamycin nephrosis and control rats.
• Measured mitochondrial iron concentration in renal cortical mitochondria.
• Administered acute iron loading to normal rats to study its effects on kidney function and mitochondrial parameters.

Main Results:

• Rats with adriamycin nephrosis exhibited increased state 4 (resting) respiration and elevated mitochondrial iron concentration compared to controls.
• Rates of respiration and proteinuria severity correlated with mitochondrial iron concentration.
• Acute iron loading impaired creatinine clearance and increased kidney weight but did not significantly alter mitochondrial respiration rates or cause mitochondrial fragility.

Conclusions:

• Resting mitochondrial respiration increases in nephrotic rats proportionally to mitochondrial iron accumulation.
• Changes in mitochondrial oxygen consumption are not the primary event in the tubular cell injury associated with iron loading in this model.