Related Experiment Video
Updated: Apr 29, 2026
06:14
Assessment of Mitochondrial Fission/Fusion Dynamics in Kidney Proximal Tubular Cells
Published on: November 14, 2025
803
Methylmalonic acidemia: a megamitochondrial disorder affecting the kidney
Zsuzsanna K Zsengellér1, Nika Aljinovic, Lisa A Teot
1Molecular Medicine, Beth Israel Deaconess Medical Center-Harvard Medical School, Boston, MA, USA, zzsengel@bidmc.harvard.edu.
Pediatric Nephrology (Berlin, Germany)
|May 29, 2014
Summary
Methylmalonic acidemia (MMA) causes chronic kidney disease due to mitochondrial dysfunction in proximal tubules. Therapies targeting mitochondrial function may treat this MMA-related kidney complication.
Area of Science:
- Biochemistry
- Nephrology
- Metabolic disorders
Background:
- Methylmalonic acidemia (MMA) is a metabolic disorder often caused by mutations in the methylmalonyl-CoA mutase (MUT) enzyme.
- Improved survival in MMA patients highlights the increasing prevalence of chronic kidney disease (CKD) as a complication.
- The exact renal pathology in MMA remains poorly understood.
Observation:
- A 19-year-old patient with mut MMA and end-stage renal disease underwent combined liver-kidney transplantation.
- Kidney tissue analysis included light microscopy, histochemistry, and ultrastructural studies.
- The study examined the native kidney prior to transplantation.
Findings:
- Renal parenchyma showed interstitial fibrosis, chronic inflammation, and tubular atrophy.
- Proximal tubules contained enlarged mitochondria with diminished cristae and reduced electron transport chain enzyme activity (cytochrome c oxidase, NADH).
- Electron microscopy confirmed loss of cytochrome c activity in these megamitochondria.
Implications:
- MMA-related CKD is characterized by proximal tubule megamitochondria and electron transport chain dysfunction.
- These findings suggest potential therapeutic strategies targeting mitochondrial function for MMA-associated kidney disease.
- Further research into mitochondrial pathways could lead to novel treatments for metabolic disorder complications.
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