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ADP and ATP Promote Mitochondrial Calcium Capacity Through Distinct Roles
Author(s) -
Deline Marshall,
Grashei Martin,
Heijster Frits,
Schilling Franz,
Straub Joshua,
Fromme Tobias
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02285
Subject(s) - adenylate kinase , mitochondrion , biochemistry , mitochondrial permeability transition pore , oxidative phosphorylation , atp–adp translocase , calcium , adenosine triphosphate , bioenergetics , biology , microbiology and biotechnology , chemistry , inner mitochondrial membrane , enzyme , apoptosis , organic chemistry , programmed cell death
The ratio of ADP and ATP is a natural indicator of cellular bioenergetic state, as such these analytes have become prominent factors in metabolism research. Beyond mitochondrial oxidative phosphorylation and ATPase activities, ADP and ATP act as steric regulators of enzymes, e.g. cytochrome C oxidase, and are major factors in mitochondrial calcium storage potential. Consideration of all routes of adenylate conversion is critical to understanding the role of each individual adenylate in the realm of mitochondrial function. Mitochondrial Adenylate Kinase activity dismutates ADP into ATP and AMP via a reversible reaction. Through the use of an Adenylate Kinase inhibitor we have noted that this enzymatic activity drives stark differences in the adenylate profile of isolated mitochondria when measured by 31‐P magnetic resonance spectroscopy. These differences are further noted when the Adenylate Kinase reverse reaction is blocked by calcium. Additionally, by utilizing endogenous mitochondrial Adenylate Kinase activity, we identified distinct roles for ADP and ATP in promoting mitochondrial calcium capacity. These roles are such that ADP provides a defense against permeability transition, while ATP contributes to calcium storage through the formation of dense calcium phosphate granules. Our findings showcase how adenylate kinases elicit considerable impact on the outcome of a variety of mitochondrial assays through their drastic manipulation of the adenylate profile. Cytochrome c oxidase activity, P/O ratio, and mitochondrial calcium dynamics were all affected by Adenylate Kinase activity. Of particular note, it was revealed that ATP is required for a particularly dense form of mitochondrial amorphous calcium phosphate, which in the future may further entangle mitochondria with physiological calcium events.