Mitochondrial Medicine: The Central Role of Cellular Energetic Depression and Mitochondria in Cell Pathophysiology

Atrophic gastritis: deficient complex I of the respiratory chain in the mitochondria of corpus mucosal cells

“…13 Recent data aim at mitochondria as key organelles in regulation of expression of the hypoxia-inducible factor-1α (HIF-1α), which is responsible for shifting metabolism from OXPHOS to glycolysis, a characteristic change in the tumor cell. This shift is controlled by multiple means including the effects of ROS (see review 14 ) and mitochondrial succinate metabolism. 15,16 Along with these changes, as a consequence of upregulation of antiapoptotic and downregulation of proapoptotic proteins, mitochondria are deprived of their effi cacy in impelling apoptosis, which favors unlimited proliferation of the cancer cells.…”

Impaired Regulation of Brain Mitochondria by Extramitochondrial Ca2+ in Transgenic Huntington Disease Rats

“…Compared with WT, Ca 2ϩ -induced inhibition of respiration of htt 51Q mitochondria was less sensitive to ruthenium red (RR), indicating the involvement of extramitochondrial Ca 2ϩ . In summary, our data suggest that mitochondriotoxic actions of htt 51Q might be realized by affecting the regulatory Ca 2ϩ binding sites of mitochondrial carrier proteins like aralar and the PT pore, finally leading to energetic depression (6,24), mitochondrial cell death, and atrophy of affected tissues (6).…”

“…Htt 51Q -dependent changes of mitochondrial regulation may uncover important pathophysiological consequences. For instance, decreased Ca 2ϩ thresholds of htt expQ mitochondria for undergoing PT might be responsible for accelerated mitochondrial cell death, in particular under conditions of elevated cytosolic Ca 2ϩ concentrations seen in HD (6). Moreover impairments of HD mitochondria may limit the cellular function also at physiological Ca 2ϩ levels.…”

“…for maximum effects of CsA, the presence of ADP and Mg 2ϩ is required. 6 Thus, CsA effects on htt 51Q mitochondria were studied in Mg 2ϩ and ADP-containing medium B. Again htt 51Q mitochondria showed their typical features as a low Ca 2ϩ uptake rate, a reduced capacity of Ca 2ϩ accumulation, and an early progression to PT (Fig.…”

Mitochondrial function in heart and kidney of spontaneously hypertensive rats: influence of captopril treatment

“…However, surprisingly, relative little interest was focused to hypertension-induced alterations in cellular energetics (Seppet et al 2007), particularly to changes in function of the mitochondria that occur parallel in the heart and kidney (De Cavanagh et al 2005). But, unfortunately, even the few available studies often present opposite results or conclusions (Roman et al 1992, Postnova et al 2007.…”