The intracellular production and transport of energetic substrate adenosine triphosphate (ATP) produced by mitochondria is dependent on multiple factors. These include local metabolic demand, mitochondrial motility and intracellular location, mitochondrial intermembrane potential, bioenergy substrate diffusion within the cell cytosol, and energy transport to the cell nucleus, which itself does not contain any mitochondria. Herein, we demonstrate via cell-based experiment and scaling argument that intracellular bioenergy transport is readily compartmentalized into perinuclear and peripheral regions of the cell. We draw on direct fluorescence-based measurement of quantum dot tracking, high-resolution respirometry, mitochondrial dynamics, and intermembrane potential to assess intracellular quantum dot diffusion to define the intracellular milieu for small molecule transport, and chemical perturbations which challenge cells by altering bioenergetics states. We identify a heterogeneous environment for intracellular bioenergy transport, with a dominant feature being present: the intracellular bioenergy distribution in response to pharmacologically induced cell challenge is determined to be preservation of perinuclear mitochondrial ATP-linked respiration in order to preserve, maintain, or otherwise support bioenergy delivery to meet the metabolic requirements of the cell nucleus whereas there is a decrement in bioenergetic capacity in the cell periphery. This dynamic effect of motile intracellular bioenergy production yields efficient transport of ATP in the maintenance of cellular health.

References

References
1.
Knowles
,
J. R.
,
1980
, “
Enzyme-Catalyzed Phosphoryl Transfer Reactions
,”
Ann. Rev. Biochem.
,
49
(
1
), pp.
877
919
.
2.
Dzeja
,
P. P.
,
Bortolon
,
R.
,
Perez-Terzic
,
C.
,
Holmuhamedov
,
E. L.
, and
Terzic
,
A.
,
2002
, “
Energetic Communication Between Mitochondria and Nucleus Directed by Catalyzed Phosphotransfer
,”
Proc. Natl. Acad. Sci. U.S.A.
,
99
(
15
), pp.
10156
10161
.
3.
Kushnareva
,
Y.
, and
Newmeyer
,
D. D.
,
2010
, “
Bioenergetics and Cell Death
,”
Ann. N. Y. Acad. Sci.
,
1201
, pp.
50
57
.
4.
Perry
,
S. W.
,
Norman
,
J. P.
,
Barbieri
,
J.
,
Brown
,
E. B.
, and
Gelbard
,
H. A.
,
2011
, “
Mitochondrial Membrane Potential Probes and the Proton Gradient: A Practical Usage Guide
,”
Biotechniques
,
50
(
2
), pp.
98
115
.
5.
Sobolewski
,
P.
,
Kandel
,
J.
, and
Eckmann
,
D. M.
,
2012
, “
Air Bubble Contact With Endothelial Cells Causes a Calcium-Independent Loss in Mitochondrial Membrane Potential
,”
PLoS One
,
7
(
10
), p.
e47254
.
6.
Lionetti
,
L.
,
Iossa
,
S.
,
Brand
,
M. D.
, and
Liverini
,
G.
,
1996
, “
Relationship Between Membrane Potential and Respiration Rate in Isolated Liver Mitochondria From Rats Fed an Energy Dense Diet
,”
Mol. Cell Biochem.
,
158
(
2
), pp.
133
138
.
7.
Hubley
,
M. J.
,
Moerland
,
T. S.
, and
Rosanske
,
R. C.
,
1995
, “
Diffusion Coefficients of Atp and Creatine Phosphate in Isolated Muscle: Pulsed Gradient 31p Nmr of Small Biological Samples
,”
NMR Biomed.
,
8
(
2
), pp.
72
78
.
8.
Kandel
,
J.
,
Chou
,
P.
, and
Eckmann
,
D. M.
,
2015
, “
Automated Detection of Whole-Cell Mitochondrial Motility and Its Dependence on Cytoarchitectural Integrity
,”
Biotechnol. Bioeng.
,
112
(
7
), pp.
1395
1405
.
9.
Jang
,
D. H.
,
Seeger
,
S. C.
,
Grady
,
M. E.
,
Shofer
,
F. S.
, and
Eckmann
,
D. M.
,
2017
, “
Mitochondrial Dynamics and Respiration Within Cells With Increased Open Pore Cytoskeletal Meshes
,”
Biol. Open
,
6
(
12
), pp.
1831
1839
.
10.
Barel
,
O.
,
Malicdan
,
M. C.
,
Ben-Zeev
,
B.
,
Pri-Chen
,
H.
,
Stephen
,
J.
,
Castro
,
I. G.
,
Metz
,
J.
,
Atawa
,
O.
,
Moshkovitz
,
S.
,
Ganelin
,
E.
,
Barshack
,
I.
,
Polak-Charcon
,
S.
,
Nass
,
D.
,
Marek-Yagel
,
D.
,
Amariglio
,
N.
,
Shalva
,
N.
,
Vilboux
,
T.
,
Ferreira
,
C.
,
Pode-Shakked
,
B.
,
Heimer
,
G.
,
Hoffmann
,
C.
,
Yardeni
,
T.
,
Nissenkorn
,
A.
,
Avivi
,
C.
,
Eyal
,
E.
,
Kol
,
N.
,
Saar
,
E. G.
,
Wallace
,
D. C.
,
Gahl
,
W. A.
,
Rechavi
,
G.
,
Schrader
,
M.
,
Eckmann
,
D. M.
, and
Anikster
,
Y.
,
2017
, “
Stuck on the Tracks: Deleterious Mutations in TRAK1 Cause Severe Fatal Encephalopathy With Cerebral Inclusion Bodies
,”
Brain
,
140
(
3
), pp.
568
581
.
11.
Grady
,
M. E.
,
Composto
,
R. J.
, and
Eckmann
,
D. M.
,
2016
, “
Cell Elasticity With Altered Cytoskeletal Architectures Across Multiple Cell Types
,”
J. Mech. Behav. Biomed. Mater.
,
61
, pp.
197
207
.
12.
Kandel
,
J.
,
Picard
,
M.
,
Wallace
,
D. C.
, and
Eckmann
,
D. M.
,
2017
, “
Progressive Increase in mtDNA 3243A>G Heteroplasmy is Associated With Nonlinear Alterations in Cytoskeletal Protein Expression and Cell Mechanics
,”
J. R. Soc., Interface
,
14
(
131
), p.
20170071
.
13.
Kandel
,
J.
,
Angelin
,
A. A.
,
Wallace
,
D. C.
, and
Eckmann
,
D. M.
,
2016
, “
Mitochondrial Respiration is Sensitive to Cytoarchitectural Breakdown
,”
Integr. Biol.
,
8
(
11
), pp.
1170
1182
.
14.
Grady
,
M. E.
,
Parrish
,
E.
,
Caporizzo
,
M. A.
,
Seeger
,
S. C.
,
Composto
,
R. J.
, and
Eckmann
,
D. M.
,
2017
, “
Intracellular Nanoparticle Dynamics Affected by Cytoskeletal Integrity
,”
Soft Matter
,
13
(
9
), pp.
1873
1880
.
15.
Flamholz
,
A.
,
Phillips
,
R.
, and
Milo
,
R.
,
2014
, “
The Quantified Cell
,”
Mol. Biol. Cell
,
25
(
22
), pp.
3497
3500
.
16.
Sobolewski
,
P.
,
Kandel
,
J.
,
Klinger
,
A. L.
, and
Eckmann
,
D. M.
,
2011
, “
Air Bubble Contact With Endothelial Cells In Vitro Induces Calcium Influx and IP3-Dependent Release of Calcium Stores
,”
Am. J. Physiol.-Cell Physiol.
,
301
(
3
), pp.
C679
C686
.
17.
Jang
,
D. H.
,
Greenwood
,
J. C.
,
Owiredu
,
S.
,
Ranganathan
,
A.
, and
Eckmann
,
D. M.
,
2017
, “
Mitochondrial Networking in Human Blood Cells With Application in Acute Care Illnesses
,”
Mitochondrion
(epub).
18.
Jang
,
D. H.
,
Khatri
,
U. G.
,
Mudan
,
A.
,
Love
,
J. S.
,
Owiredu
,
S.
, and
Eckmann
,
D. M.
,
2018
, “
Translational Application of Measuring Mitochondrial Functions in Blood Cells Obtained From Patients With Acute Poisoning
,”
J. Med. Toxicol.
,
14
(
2
), pp.
144
151
.
19.
Jang
,
D. H.
,
Owiredu
,
S.
,
Ranganathan
,
A.
, and
Eckmann
,
D. M.
,
2018
, “
Acute Decompression Alters Mitochondrial Dynamics and Cellular Respiration
,”
Am. J. Physiol. Cell Physiol.
,
315
(
5
), pp.
C699
C705
.
20.
Li
,
H.
,
Dou
,
S. X.
,
Liu
,
Y. R.
,
Li
,
W.
,
Xie
,
P.
,
Wang
,
W. C.
, and
Wang
,
P. Y.
,
2015
, “
Mapping Intracellular Diffusion Distribution Using Single Quantum Dot Tracking: Compartmentalized Diffusion Defined by Endoplasmic Reticulum
,”
J. Am. Chem. Soc.
,
137
(
1
), pp.
436
444
.
21.
Azarashvili
,
T. S.
,
Odinokova
,
I. V.
,
Krestinina
,
O. V.
,
Baburina
,
Y. L.
,
Grachev
,
D. E.
,
Teplova
,
V. V.
, and
Holmuhamedov
,
E. L.
,
2011
, “
Role of Phosphoirylation of Porine Proteins in Regulation of Mitochondrial Outer Membrane Under Normal Conditions and Alcohol Intoxication
,”
Biol. Membr.
,
28
(
1
), pp.
14
24
.
You do not currently have access to this content.