PMID- 35011693
OWN - NLM
STAT- MEDLINE
DCOM- 20220303
LR  - 20240226
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Dec 31
TI  - Substrate- and Calcium-Dependent Differential Regulation of Mitochondrial 
      Oxidative Phosphorylation and Energy Production in the Heart and Kidney.
LID - 10.3390/cells11010131 [doi]
LID - 131
AB  - Mitochondrial dehydrogenases are differentially stimulated by Ca(2+). Ca(2+) has 
      also diverse regulatory effects on mitochondrial transporters and other enzymes. 
      However, the consequences of these regulatory effects on mitochondrial oxidative 
      phosphorylation (OxPhos) and ATP production, and the dependencies of these 
      consequences on respiratory substrates, have not been investigated between the 
      kidney and heart despite the fact that kidney energy requirements are second only 
      to those of the heart. Our objective was, therefore, to elucidate these 
      relationships in isolated mitochondria from the kidney outer medulla (OM) and 
      heart. ADP-induced mitochondrial respiration was measured at different CaCl(2) 
      concentrations in the presence of various respiratory substrates, including 
      pyruvate + malate (PM), glutamate + malate (GM), alpha-ketoglutarate + malate 
      (AM), palmitoyl-carnitine + malate (PCM), and succinate + rotenone (SUC + ROT). 
      The results showed that, in both heart and OM mitochondria, and for most complex 
      I substrates, Ca(2+) effects are biphasic: small increases in Ca(2+) 
      concentration stimulated, while large increases inhibited mitochondrial 
      respiration. Furthermore, significant differences in substrate- and 
      Ca(2+)-dependent O(2) utilization towards ATP production between heart and OM 
      mitochondria were observed. With PM and PCM substrates, Ca(2+) showed more 
      prominent stimulatory effects in OM than in heart mitochondria, while with GM and 
      AM substrates, Ca(2+) had similar biphasic regulatory effects in both OM and 
      heart mitochondria. In contrast, with complex II substrate SUC + ROT, only 
      inhibitory effects on mitochondrial respiration was observed in both the heart 
      and the OM. We conclude that the regulatory effects of Ca(2+) on mitochondrial 
      OxPhos and ATP synthesis are biphasic, substrate-dependent, and tissue-specific.
FAU - Zhang, Xiao
AU  - Zhang X
AD  - Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI 
      53226, USA.
FAU - Tomar, Namrata
AU  - Tomar N
AD  - Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI 
      53226, USA.
FAU - Kandel, Sunil M
AU  - Kandel SM
AD  - Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI 
      53226, USA.
FAU - Audi, Said H
AU  - Audi SH
AD  - Department of Biomedical Engineering, Marquette University, Milwaukee, WI 53223, 
      USA.
FAU - Cowley, Allen W Jr
AU  - Cowley AW Jr
AD  - Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI 
      53226, USA.
AD  - Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
FAU - Dash, Ranjan K
AU  - Dash RK
AD  - Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI 
      53226, USA.
AD  - Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI 
      53226, USA.
AD  - Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
LA  - eng
GR  - R01 HL151587/HL/NHLBI NIH HHS/United States
GR  - P01 HL116264/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20211231
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - Cell Respiration
MH  - *Energy Metabolism
MH  - Kidney/*metabolism
MH  - Mitochondria, Heart/*metabolism
MH  - Models, Biological
MH  - *Oxidative Phosphorylation
MH  - Oxygen Consumption/physiology
MH  - Rats, Sprague-Dawley
MH  - Substrate Specificity
MH  - Time Factors
MH  - Rats
PMC - PMC8750792
OTO - NOTNLM
OT  - ATP synthesis
OT  - calcium regulation
OT  - energy metabolism
OT  - mitochondrial respiration
OT  - oxidative phosphorylation
OT  - respiratory control
OT  - substrate utilization
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper. The authors declare no conflict of interest.
EDAT- 2022/01/12 06:00
MHDA- 2022/03/04 06:00
PMCR- 2021/12/31
CRDT- 2022/01/11 01:15
PHST- 2021/12/10 00:00 [received]
PHST- 2021/12/26 00:00 [revised]
PHST- 2021/12/28 00:00 [accepted]
PHST- 2022/01/11 01:15 [entrez]
PHST- 2022/01/12 06:00 [pubmed]
PHST- 2022/03/04 06:00 [medline]
PHST- 2021/12/31 00:00 [pmc-release]
AID - cells11010131 [pii]
AID - cells-11-00131 [pii]
AID - 10.3390/cells11010131 [doi]
PST - epublish
SO  - Cells. 2021 Dec 31;11(1):131. doi: 10.3390/cells11010131.