Different Metabolic Properties of Mitochondrial Oxidative Phosphorylation in Different Cell Types ‐ Important Implications for Mitochondrial Cytopathies

Abstract

The metabolic and functional diversity of animal mitochondria caused by different mitochondrial compositions due to tissue‐specific mitochondrial pathways and tissue‐specific differences in expression of isoforms of subunits of enzymes participating in oxidative phosphorylation will be reviewed here. Applying the concept of metabolic control analysis, the relevance of this diversity for the explanation of tissue‐specific effects observed in mitochondrial diseases with homoplasmic mitochondrial DNA mutations and nuclear‐encoded respiratory chain defects is discussed.

Tissue-specific differences in mitochondrial activity and biogenesis

“…These differences are probably reflecting the different metabolic roles each tissue plays in the organism and the contribution of OXPHOS to the main metabolic pathways, namely, cardiomyocyte mitochondria are specialized in ATP production mostly by fatty-acid oxidation, in liver organelles several aspects of the urea cycle are enhanced, kidney seems to rely on the metabolism of some amino acids and brain is specialized in neurotransmitter metabolism and reactive oxygen species (ROS) detoxification (Johnson et al, 2007a). It is important to define the tissue-specific characteristics of the OXPHOS capacity as a contribution to the understanding of why some tissues are more affected than others in mitochondrial disorders due to a primary malfunction of the OXPHOS system (Kunz, 2003;Rossignol et al, 1999). The aforementioned system is unique in the cell as its biogenesis requires the coordinated expression of both mitochondrial and nuclear genomes.…”

“…Each animal organ or tissue has a different metabolic profile and variable energetic demands due to the inherently different functions or, in a same tissue, to changes in ATP demand due to physiological or pathological conditions (Kunz, 2003;Leary et al, 1998;Leverve and Fontaine, 2001;Pfeiffer et al, 2001). Thus, it is reasonable to expect that their mitochondrial respiratory capacity would also be different and related to variations between tissues in mitochondrial function, protein composition and morphology (Benard et al, 2006;Johnson et al, 2007a,b;Mootha et al, 2003;Pagliarini et al, 2008).…”

Rat diaphragm mitochondria have lower intrinsic respiratory rates than mitochondria in limb muscles

“…We found that the content of complexes I and II and complex I activity were not different between TS and diaphragm. Others demonstrated that mitochondrial differences may result from tissue-specific mitochondrial pathways and tissue-specific differences in the expression of isoforms of subunits of oxidative phosphorylation enzymes (21). It follows then that the content of respiratory complexes may not be solely responsible for the differences in respiration rates.…”

Cell and animal models of mtDNA biology: progress and prospects

“…It is therefore dangerous to assume that simply removing mitochondria from glycolytic cells for use in biochemical assays somehow frees them of a glycolytic origin. On the contrary, it is already known that mitochondria isolated from different tissues behave differently (64). It is also possible that mitigating nuclear factors render some cell lines less likely to manifest mitochondrial deficits (44)…”