Welcome to the Introductory page for Jack Kennell and lab co-workers at Saint Louis University.
We are interested in all things mitochondrial, especially mitochondrial genetics of filamentous fungi. Within this website you can find information describing fungal mitochondrial genomes, mutants, extrachromosomal plasmids, as well as nuclear genes involved in mitochondrial function. Particular emphasis is placed on the ascomycete, Neurospora crassa.
The site is divided into three major areas:
Fungal Respiratory Pathways
The production of ATP coupled to electron transport is an invariant feature of mitochondria. In animal mitochondria, the respiratory chain begins with electrons being transferred from NADH to complex I (NADH:ubiquinone oxidoreductase) or from the tricarboxylic acid cycle intermediate succinate to complex II (succinate:ubiquinone oxidoreductase). Electrons are transferred via ubiquinones, complex III (ubiquinol:cytochrome c oxidoreductase), cytochrome c, complex IV (cytochrome c oxidase) and finally to molecular oxygen to give water. Although this respiratory pathway is present in most fungal mitochondria, a few fungi, such as Saccharomyces cerevisiae and Schizosaccharomyces pombe, lack complex I. More commonly, however, fungi have additional components, such as alternative NADH dehydrogenases and/or an alternative terminal oxidase (reviewed by Joseph-Horne et al. 2001).
Complex I is a large multisubunit complex that spans the inner mitochondrial membrane and includes both nuclear- and mitochondrial-encoded gene products. In contrast, alternative dehydrogenases are encoded by single nuclear genes and can be located on either the matrix (internal) or intermembrane space (external) side of the inner membrane. Having both internal and external alternative dehydrogenases allow electrons to enter the respiratory chain from either side of the membrane and it is thought that their use may help reduce the production of reactive oxygen species (ROS) generated by the standard respiratory pathway (Joseph-Horne at al. 2001).
The alternative oxidase (AOD) is a nuclear-encoded secondary terminal oxidase present in plants and most fungi (S. cerevisiae and S. pombe are notable exceptions). Although there are differences between fungal and plant alternative oxidases—the fungal AOD is regulated by AMP, ADP and GDP (Vanderleyden et al. 1980; Michea-Hamzehpour and Turian 1987), while the plant AOD is stimulated by a-keto acids (Rhoads et al. 1998)—they appear to function in a similar manner (Umbach and Siedow 2000). The AOD is located in the inner mitochondrial membrane and catalyzes the reduction of oxygen to water after receiving electrons directly from reduced ubiquinone, circumventing complex III and complex IV. Consequently, cells expressing AOD are insensitive to respiratory inhibitors such as antimycin A and cyanide and ATP production continues due to proton pumping through complex I.
In most systems studied, alternative oxidases are subject to multiple forms of regulation and generally operate only under conditions that inhibit the standard electron transport. Induction of the alternative oxidase could be particularly important for fungal plant pathogens that are exposed to inhibitors of the cytochrome oxidase pathway such as NO released by plants expressing the hypersensitive response (Joseph-Horne et al. 2001). Finally, other studies have found that certain filamentous fungi (e.g. Fusarium oxysporum), have the ability to metabolize nitrate to N2O (denitrification), a process that occurs in the mitochondrion and is coupled to ATP synthesis (Kobayashi et al. 1996). Remarkably, when under anoxic conditions these denitrifying fungi are also able to ferment ammonia (Zhou et al. 2002).
Taken together, these studies indicate that fungal mitochondria include several components that are not found in animal cells. The additional components provide greater versatility in aerobic respiration and enable fungi to adjust their metabolic capacity when encountering different energy sources or when in the presence of inhibitors of the cytochrome oxidase pathway.
REFERENCES
| Joseph-Horne T, Hollomon DW and Wood PM (2001). Fungal respiration: a fusion of standard and alternative components. Biochim Biophys Acta 1504: 179-195. |
| Kobayashi M, Matsuo Y, Takimoto A, Suzuki S, Maruo F and Shoun H (1996). Denitrification, a novel type of respiratory metabolism in fungal mitochondrion. J Biol Chem 271: 16263-16267. |
| Michea-Hamzehpour M and Turian G (1987). GMP-stimulation of the cyanide-insensitive mitochondrial respiration in heat-shocked conidia of Neurospora crassa. Experientia 43: 439-440. |
| Umbach AL and Siedow JN (2000). The cyanide-resistant alternative oxidases from the fungi Pichia stipitis and Neurospora crassa are monomeric and lack regulatory features of the plant enzyme. Arch Biochem Biophys 378: 234-245. |
| Vanderleyden J, Peeters C, Verachtert H and Bertrand H (1980). Substrate kinetics of the alternative oxidase of Neurospora crassa. Biochem J 186: 1009-1011. |
| Zhou Z, Takaya N, Nakamura A, Yamaguchi M, Takeo K and Shoun H (2002). Ammonia fermentation, a novel anoxic metabolism of nitrate by fungi. J Biol Chem 277: 1892-1896. |
If you have any addendums or corrections to the information presented on this website please contact Dr. Jack Kennell at kennellj@slu.edu. Thank you.
