Objectives: 

The structural organization of the mitochondrial oxidative phosphorylation system still remains a controversial issue. Studies performed by blue native gel electrophoresis (BNGE) have shown how mitochondrial respiratory complexes could assembly into efficient supramolecular associations or supercomplexes, which behaves as functional and physiological entities named "respirasomes". Recent investigations have revealed the presence of Coenzyme Q (CoQ) in some supercomplexes variants. Whether these findings have some implication in the pathophysiology of CoQ deficiency syndrome is unknown. Moreover, if some CoQ deficient cells exhibit instability of mitochondrial supercomplexes, those cells may respond differently in terms of protection mechanisms like mitophagy and mitochondrial biogenesis.

Materials: 

We have generated a new genetically modified mouse model with wide spread CoQ deficiency. The following parameters were evaluated in tissues and mitochondria from wild-type and CoQ deficient mice: supercomplexes formation pattern through BNGE; activities of the CoQ-dependent mitochondrial complexes by spectrophotometry; quantification of mtDNA by RT-PCR; and mitochondrial biogenesis and mitophagy by western blot analysis of key proteins.

Results: 

CoQ deficient mice exhibit a profound instability of some supercomplexes, which is especially evident in the brain. CoQ deficient mice also show tissue-specific differences in the CoQ-dependent complexes activities, mitochondrial biogenesis and mitophagy, which may explain the encephalopathy that suffer from this mouse model.

Conclusions: 

This study is able to demonstrate, for the first time, that deficiency of CoQ causes instability of particular mitochondrial supercomplexes. This new molecular aspect associated to CoQ deficiency syndrome, together with the tissue-specific protection mechanisms, may be relevant to understand the clinical heterogeneity of the disease. In addition, our data may be important for the elaboration of new therapeutic strategies.