PMID- 35499238
OWN - NLM
STAT- MEDLINE
DCOM- 20220623
LR  - 20220708
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 323
IP  - 1
DP  - 2022 Jul 1
TI  - Regulation of kidney mitochondrial function by caloric restriction.
PG  - F92-F106
LID - 10.1152/ajprenal.00461.2021 [doi]
AB  - Caloric restriction (CR) prevents obesity and increases resilience against 
      pathological stimuli in laboratory rodents. At the mitochondrial level, 
      protection promoted by CR in the brain and liver is related to higher Ca(2+) 
      uptake rates and capacities, avoiding Ca(2+)-induced mitochondrial permeability 
      transition. Dietary restriction has also been shown to increase kidney resistance 
      against damaging stimuli; if these effects are related to similar mitochondrial 
      adaptations has not been uncovered. Here, we characterized changes in 
      mitochondrial function in response to 6 mo of CR in rats and measured 
      bioenergetic parameters, redox balance, and Ca(2+) homeostasis. CR promoted an 
      increase in succinate-supported mitochondrial oxygen consumption rates. Although 
      CR prevents mitochondrial reactive oxygen species production in many tissues, in 
      kidney, we found that mitochondrial H(2)O(2) release was enhanced in a 
      succinate-dependent manner. Surprisingly, and opposite to the effects observed in 
      the brain and liver, mitochondria from CR animals were more prone to 
      Ca(2+)-induced mitochondrial permeability transition, in a manner reversed by the 
      antioxidant dithiothreitol. CR mitochondria also displayed higher Ca(2+) uptake 
      rates, which were not accompanied by changes in Ca(2+) efflux rates or related to 
      altered inner mitochondrial membrane potentials or amounts of the mitochondrial 
      Ca(2+) uniporter. Instead, increased mitochondrial Ca(2+) uptake rates in CR 
      kidneys correlated with loss of mitochondrial Ca(2+) uptake protein 2 (MICU2), a 
      mitochondrial Ca(2+) uniporter modulator. Interestingly, MICU2 is also modulated 
      by CR in the liver, suggesting that it has a broader diet-sensitive regulatory 
      role controlling mitochondrial Ca(2+) homeostasis. Together, our results 
      highlight the organ-specific bioenergetic, redox, and ionic transport results of 
      CR, with some unexpected deleterious effects in the kidney.NEW & NOTEWORTHY 
      Prevention of obesity through caloric restriction (CR) is well known to protect 
      many tissues but has been poorly studied in kidneys. Here, we determined the 
      effects of long-term CR in rat kidney mitochondria, which are central players in 
      energy metabolism and aging. Surprisingly, we found that the diet increased 
      mitochondrial reactive oxygen production and permeability transition. This 
      suggests that the kidneys respond differently to restricted diets and may be more 
      susceptible under CR.
FAU - Serna, Julian D C
AU  - Serna JDC
AUID- ORCID: 0000-0002-2285-5769
AD  - Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Amaral, Andressa G
AU  - Amaral AG
AD  - Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, 
      Universidade de Sao Paulo, Sao Paulo, Brazil.
FAU - Caldeira da Silva, Camille C
AU  - Caldeira da Silva CC
AD  - Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Munhoz, Ana C
AU  - Munhoz AC
AUID- ORCID: 0000-0002-7484-0518
AD  - Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Vilas-Boas, Eloisa A
AU  - Vilas-Boas EA
AUID- ORCID: 0000-0003-1565-1618
AD  - Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Menezes-Filho, Sergio L
AU  - Menezes-Filho SL
AD  - Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Kowaltowski, Alicia J
AU  - Kowaltowski AJ
AUID- ORCID: 0000-0002-3807-2419
AD  - Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao 
      Paulo, Brazil.
LA  - eng
SI  - figshare/10.6084/m9.figshare.19604455
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220502
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Succinates)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Animals
MH  - *Caloric Restriction
MH  - *Hydrogen Peroxide/metabolism
MH  - Kidney/metabolism
MH  - Mitochondria/metabolism
MH  - Mitochondrial Proteins/metabolism
MH  - Obesity/metabolism
MH  - Rats
MH  - Succinates/metabolism
OTO - NOTNLM
OT  - calcium
OT  - calorie restriction
OT  - kidney
OT  - mitochondria
OT  - reactive oxygen species
EDAT- 2022/05/03 06:00
MHDA- 2022/06/24 06:00
CRDT- 2022/05/02 07:53
PHST- 2022/05/03 06:00 [pubmed]
PHST- 2022/06/24 06:00 [medline]
PHST- 2022/05/02 07:53 [entrez]
AID - 10.1152/ajprenal.00461.2021 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2022 Jul 1;323(1):F92-F106. doi: 
      10.1152/ajprenal.00461.2021. Epub 2022 May 2.