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The Mitochondrial ATP Synthase in Cardiac Biology and Disease.

紀錄類型:	書目-語言資料,手稿 : Monograph/item
正題名/作者:	The Mitochondrial ATP Synthase in Cardiac Biology and Disease./
作者:	Wittig, Andre.
面頁冊數:	1 online resource (140 pages)
附註:	Source: Dissertations Abstracts International, Volume: 84-08, Section: B.
Contained By:	Dissertations Abstracts International84-08B.
標題:	Cellular biology. -
電子資源:	click for full text (PQDT)
ISBN:	9798368482644

The Mitochondrial ATP Synthase in Cardiac Biology and Disease.
Wittig, Andre.

The Mitochondrial ATP Synthase in Cardiac Biology and Disease. - 1 online resource (140 pages)

Source: Dissertations Abstracts International, Volume: 84-08, Section: B.

Thesis (Ph.D.)--Albert Einstein College of Medicine, 2024.

Includes bibliographical references

The mitochondrial ATP synthase generates the majority of the ATP in mammalian cells. To assess the role of the ATP synthase under energetically demanding conditions in vivo, we created mice deficient in this 29-subunit complex, specifically in cardiomyocytes starting in adulthood. To accomplish this we deleted the nuclear gene encoding ATP5L, a subunit required for assembly of new complexes. Consistent with its previously measured half-life of 33-days, ATP synthase abundance progressively decreased in knockout mice (KO) to ~10% of that in controls by 12-weeks post-deletion. Despite this, KOs appeared healthy and exhibited normal cardiac function. Between 12-16 weeks post-deletion, however, 100% of KOs developed heart failure and died. At 12-weeks post-deletion, marked mitochondrial cristae abnormalities were evident. Moreover, despite ATP synthase levels being decreased ~90%, mitochondrial ATP synthesis rates and steady state ATP levels were decreased only ~50%. Glycolysis, glucose oxidation, and the malate-aspartate shuttle were upregulated as compensatory mechanisms. Mechanistically, KOs exhibited marked increases in the abundance of the mitochondrial calcium uniporter, BAX, several mitochondrial dynamics factors, and other metabolic enzymes which will be the subject of subsequent studies. We conclude that mice with marked deficiency of the mitochondrial ATP synthase in an energy demanding vital organ can live normally under unstressed conditions for several months because of multiple compensatory mechanisms.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798368482644Subjects--Topical Terms:

1148666
Cellular biology.
Subjects--Index Terms:

Mitochondrial ATP synthaseIndex Terms--Genre/Form:

554714
Electronic books.

The Mitochondrial ATP Synthase in Cardiac Biology and Disease.
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520 $a The mitochondrial ATP synthase generates the majority of the ATP in mammalian cells. To assess the role of the ATP synthase under energetically demanding conditions in vivo, we created mice deficient in this 29-subunit complex, specifically in cardiomyocytes starting in adulthood. To accomplish this we deleted the nuclear gene encoding ATP5L, a subunit required for assembly of new complexes. Consistent with its previously measured half-life of 33-days, ATP synthase abundance progressively decreased in knockout mice (KO) to ~10% of that in controls by 12-weeks post-deletion. Despite this, KOs appeared healthy and exhibited normal cardiac function. Between 12-16 weeks post-deletion, however, 100% of KOs developed heart failure and died. At 12-weeks post-deletion, marked mitochondrial cristae abnormalities were evident. Moreover, despite ATP synthase levels being decreased ~90%, mitochondrial ATP synthesis rates and steady state ATP levels were decreased only ~50%. Glycolysis, glucose oxidation, and the malate-aspartate shuttle were upregulated as compensatory mechanisms. Mechanistically, KOs exhibited marked increases in the abundance of the mitochondrial calcium uniporter, BAX, several mitochondrial dynamics factors, and other metabolic enzymes which will be the subject of subsequent studies. We conclude that mice with marked deficiency of the mitochondrial ATP synthase in an energy demanding vital organ can live normally under unstressed conditions for several months because of multiple compensatory mechanisms.
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