In vivo multiphoton imaging of mitochondrial structure and function during acute kidney injury

Andrew M. Hall, George J. Rhodes, Ruben M. Sandoval, Peter R. Corridon, Bruce Molitoris

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Mitochondrial dysfunction has been implicated in the pathogenesis of acute kidney injury due to ischemia and toxic drugs. Methods for imaging mitochondrial function in cells using confocal microscopy are well established; more recently, it was shown that these techniques can be utilized in ex vivo kidney tissue using multiphoton microscopy. We extended this approach in vivo and found that kidney mitochondrial structure and function can be imaged in anesthetized rodents using multiphoton excitation of endogenous and exogenous fluorophores. Mitochondrial nicotinamide adenine dinucleotide increased markedly in rat kidneys in response to ischemia. Following intravenous injection, the mitochondrial membrane potential-dependent dye TMRM was taken up by proximal tubules; in response to ischemia, the membrane potential dissipated rapidly and mitochondria became shortened and fragmented in proximal tubules. In contrast, the mitochondrial membrane potential and structure were better maintained in distal tubules. Changes in mitochondrial structure, nicotinamide adenine dinucleotide, and membrane potential were found in the proximal, but not distal, tubules after gentamicin exposure. These changes were sporadic, highly variable among animals, and were preceded by changes in non-mitochondrial structures. Thus, real-time changes in mitochondrial structure and function can be imaged in rodent kidneys in vivo using multiphoton excitation of endogenous and exogenous fluorophores in response to ischemia-reperfusion injury or drug toxicity.

Original languageEnglish
Pages (from-to)72-83
Number of pages12
JournalKidney International
Volume83
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Acute Kidney Injury
Kidney
Ischemia
Mitochondrial Membrane Potential
NAD
Membrane Potentials
Rodentia
Poisons
Gentamicins
Reperfusion Injury
Drug-Related Side Effects and Adverse Reactions
Confocal Microscopy
Intravenous Injections
Microscopy
Mitochondria
Coloring Agents
Pharmaceutical Preparations

Keywords

  • acute kidney injury
  • gentamicin
  • in vivo microscopy
  • ischemia
  • mitochondria
  • multiphoton imaging

ASJC Scopus subject areas

  • Nephrology

Cite this

In vivo multiphoton imaging of mitochondrial structure and function during acute kidney injury. / Hall, Andrew M.; Rhodes, George J.; Sandoval, Ruben M.; Corridon, Peter R.; Molitoris, Bruce.

In: Kidney International, Vol. 83, No. 1, 01.2013, p. 72-83.

Research output: Contribution to journalArticle

Hall, Andrew M. ; Rhodes, George J. ; Sandoval, Ruben M. ; Corridon, Peter R. ; Molitoris, Bruce. / In vivo multiphoton imaging of mitochondrial structure and function during acute kidney injury. In: Kidney International. 2013 ; Vol. 83, No. 1. pp. 72-83.
@article{a11163ab78034874abbdd91dae30c105,
title = "In vivo multiphoton imaging of mitochondrial structure and function during acute kidney injury",
abstract = "Mitochondrial dysfunction has been implicated in the pathogenesis of acute kidney injury due to ischemia and toxic drugs. Methods for imaging mitochondrial function in cells using confocal microscopy are well established; more recently, it was shown that these techniques can be utilized in ex vivo kidney tissue using multiphoton microscopy. We extended this approach in vivo and found that kidney mitochondrial structure and function can be imaged in anesthetized rodents using multiphoton excitation of endogenous and exogenous fluorophores. Mitochondrial nicotinamide adenine dinucleotide increased markedly in rat kidneys in response to ischemia. Following intravenous injection, the mitochondrial membrane potential-dependent dye TMRM was taken up by proximal tubules; in response to ischemia, the membrane potential dissipated rapidly and mitochondria became shortened and fragmented in proximal tubules. In contrast, the mitochondrial membrane potential and structure were better maintained in distal tubules. Changes in mitochondrial structure, nicotinamide adenine dinucleotide, and membrane potential were found in the proximal, but not distal, tubules after gentamicin exposure. These changes were sporadic, highly variable among animals, and were preceded by changes in non-mitochondrial structures. Thus, real-time changes in mitochondrial structure and function can be imaged in rodent kidneys in vivo using multiphoton excitation of endogenous and exogenous fluorophores in response to ischemia-reperfusion injury or drug toxicity.",
keywords = "acute kidney injury, gentamicin, in vivo microscopy, ischemia, mitochondria, multiphoton imaging",
author = "Hall, {Andrew M.} and Rhodes, {George J.} and Sandoval, {Ruben M.} and Corridon, {Peter R.} and Bruce Molitoris",
year = "2013",
month = "1",
doi = "10.1038/ki.2012.328",
language = "English",
volume = "83",
pages = "72--83",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - In vivo multiphoton imaging of mitochondrial structure and function during acute kidney injury

AU - Hall, Andrew M.

AU - Rhodes, George J.

AU - Sandoval, Ruben M.

AU - Corridon, Peter R.

AU - Molitoris, Bruce

PY - 2013/1

Y1 - 2013/1

N2 - Mitochondrial dysfunction has been implicated in the pathogenesis of acute kidney injury due to ischemia and toxic drugs. Methods for imaging mitochondrial function in cells using confocal microscopy are well established; more recently, it was shown that these techniques can be utilized in ex vivo kidney tissue using multiphoton microscopy. We extended this approach in vivo and found that kidney mitochondrial structure and function can be imaged in anesthetized rodents using multiphoton excitation of endogenous and exogenous fluorophores. Mitochondrial nicotinamide adenine dinucleotide increased markedly in rat kidneys in response to ischemia. Following intravenous injection, the mitochondrial membrane potential-dependent dye TMRM was taken up by proximal tubules; in response to ischemia, the membrane potential dissipated rapidly and mitochondria became shortened and fragmented in proximal tubules. In contrast, the mitochondrial membrane potential and structure were better maintained in distal tubules. Changes in mitochondrial structure, nicotinamide adenine dinucleotide, and membrane potential were found in the proximal, but not distal, tubules after gentamicin exposure. These changes were sporadic, highly variable among animals, and were preceded by changes in non-mitochondrial structures. Thus, real-time changes in mitochondrial structure and function can be imaged in rodent kidneys in vivo using multiphoton excitation of endogenous and exogenous fluorophores in response to ischemia-reperfusion injury or drug toxicity.

AB - Mitochondrial dysfunction has been implicated in the pathogenesis of acute kidney injury due to ischemia and toxic drugs. Methods for imaging mitochondrial function in cells using confocal microscopy are well established; more recently, it was shown that these techniques can be utilized in ex vivo kidney tissue using multiphoton microscopy. We extended this approach in vivo and found that kidney mitochondrial structure and function can be imaged in anesthetized rodents using multiphoton excitation of endogenous and exogenous fluorophores. Mitochondrial nicotinamide adenine dinucleotide increased markedly in rat kidneys in response to ischemia. Following intravenous injection, the mitochondrial membrane potential-dependent dye TMRM was taken up by proximal tubules; in response to ischemia, the membrane potential dissipated rapidly and mitochondria became shortened and fragmented in proximal tubules. In contrast, the mitochondrial membrane potential and structure were better maintained in distal tubules. Changes in mitochondrial structure, nicotinamide adenine dinucleotide, and membrane potential were found in the proximal, but not distal, tubules after gentamicin exposure. These changes were sporadic, highly variable among animals, and were preceded by changes in non-mitochondrial structures. Thus, real-time changes in mitochondrial structure and function can be imaged in rodent kidneys in vivo using multiphoton excitation of endogenous and exogenous fluorophores in response to ischemia-reperfusion injury or drug toxicity.

KW - acute kidney injury

KW - gentamicin

KW - in vivo microscopy

KW - ischemia

KW - mitochondria

KW - multiphoton imaging

UR - http://www.scopus.com/inward/record.url?scp=84871796325&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871796325&partnerID=8YFLogxK

U2 - 10.1038/ki.2012.328

DO - 10.1038/ki.2012.328

M3 - Article

VL - 83

SP - 72

EP - 83

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 1

ER -