| 1. |
- Kukat, C, et al.
(författare)
-
Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA
- 2011
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 108:33, s. 13534-13539
-
Tidskriftsartikel (refereegranskat)abstract
- Mammalian mtDNA is packaged in DNA-protein complexes denoted mitochondrial nucleoids. The organization of the nucleoid is a very fundamental question in mitochondrial biology and will determine tissue segregation and transmission of mtDNA. We have used a combination of stimulated emission depletion microscopy, enabling a resolution well below the diffraction barrier, and molecular biology to study nucleoids in a panel of mammalian tissue culture cells. We report that the nucleoids labeled with antibodies against DNA, mitochondrial transcription factor A (TFAM), or incorporated BrdU, have a defined, uniform mean size of ∼100 nm in mammals. Interestingly, the nucleoid frequently contains only a single copy of mtDNA (average ∼1.4 mtDNA molecules per nucleoid). Furthermore, we show by molecular modeling and volume calculations that TFAM is a main constituent of the nucleoid, besides mtDNA. These fundamental insights into the organization of mtDNA have broad implications for understanding mitochondrial dysfunction in disease and aging.
|
|
| 2. |
- Sterky, FH, et al.
(författare)
-
Impaired mitochondrial transport and Parkin-independent degeneration of respiratory chain-deficient dopamine neurons in vivo
- 2011
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 108:31, s. 12937-12942
-
Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction is heavily implicated in Parkinson disease (PD) as exemplified by the finding of an increased frequency of respiratory chain-deficient dopamine (DA) neurons in affected patients. An inherited form of PD is caused by impaired function of Parkin, an E3 ubiquitin ligase reported to translocate to defective mitochondria in vitro to facilitate their clearance. We have developed a reporter mouse to assess mitochondrial morphology in DA neurons in vivo and show here that respiratory chain deficiency leads to fragmentation of the mitochondrial network and to the formation of large cytoplasmic bodies derived from mitochondria. Surprisingly, the dysfunctional mitochondria do not recruit Parkin in vivo, and neither the clearance of defective mitochondria nor the neurodegeneration phenotype is affected by the absence of Parkin. We also show that anterograde axonal transport of mitochondria is impaired in respiratory chain-deficient DA neurons, leading to a decreased supply of mitochondria to the axonal terminals.
|
|
| 3. |
|
|
