Mitochondrial complex I is deficient in renal oncocytomas

Helene Simonnet1, Jocelyne Demont, Kathy Pfeiffer

  • 1CGMC (Center of Molecular and Cell Genetics), Unit 5534 of the CNRS and the University Lyon 1 Claude Bernard, Villeurbanne, France. simonnet@univ-lyon1.fr

Carcinogenesis
|July 8, 2003
PubMed

Insights

Renal oncocytomas show a specific decrease in mitochondrial complex I, unlike malignant tumors. This deficiency may drive increased mitochondria and impaired ATP production in these benign kidney tumors.

Area of Science:

  • Nephrology
  • Mitochondrial Biology
  • Oncology

Background:

  • Renal oncocytomas are benign tumors with increased mitochondria, but the functionality of their oxidative phosphorylation (OXPHOS) system is unclear.
  • Previous studies noted increased mitochondrial DNA and OXPHOS complex activity, yet functional assessment was lacking.

Purpose of the Study:

  • To investigate the functional status of mitochondrial complex I in renal oncocytomas.
  • To differentiate mitochondrial alterations in oncocytomas from those in malignant renal tumors.

Main Methods:

  • Analysis of NADH dehydrogenase activity and protein content of mitochondrial complex I in oncocytomas.
  • Comparison of complex I alterations in oncocytomas with those in malignant renal tumors.
  • Assessment of complex I activity in peritumoral tissue.

Main Results:

  • Renal oncocytomas exhibit a specific decrease in mitochondrial complex I (NADH dehydrogenase) activity and protein content.
  • In contrast, malignant renal tumors show a parallel decrease in all respiratory chain complexes.
  • Complex I activity is also moderately reduced in tissue adjacent to oncocytomas.

Conclusions:

  • Complex I deficiency is a potential early event in oncocytoma development, triggering compensatory mitochondrial biogenesis.
  • Oncocytoma represents a third type of benign tumor linked to impaired mitochondrial ATP production.
  • The findings suggest oncocytomas arise from at least two sequential alterations affecting the mitochondrial respiratory chain.

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Renal Tubule and Collecting Duct01:24

Renal Tubule and Collecting Duct

The renal tubule is divided into three parts: the proximal convoluted tubule (PCT), the Loop of Henle (LOH), and the distal convoluted tubule (DCT).
Proximal Convoluted Tubule (PCT):
The PCT is the initial segment of the renal tubule, extending from the Bowman's capsule that encloses the glomerulus. Its convoluted structure and microvilli-lined cells increase the surface area for reabsorption. The PCT reabsorbs glucose, amino acids, sodium, and water from the filtrate, ensuring essential...
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
The Inner Mitochondrial Membrane01:28

The Inner Mitochondrial Membrane

The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...