東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

The Mitochondrial ATP Synthase in Ca...

Wittig, Andre,

FindBook

Google Book

Amazon

博客來

The Mitochondrial ATP Synthase in Cardiac Biology and Disease /

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Mitochondrial ATP Synthase in Cardiac Biology and Disease // Andre Wittig.
作者:	Wittig, Andre,
面頁冊數:	1 electronic 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:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30246128
ISBN:	9798368482644

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

The Mitochondrial ATP Synthase in Cardiac Biology and Disease /Andre Wittig. - 1 electronic resource (140 pages)

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

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.

English

ISBN: 9798368482644Subjects--Topical Terms:

3172791
Cellular biology.
Subjects--Index Terms:

Mitochondrial ATP synthase

The Mitochondrial ATP Synthase in Cardiac Biology and Disease /
LDR:02786nmm a22003613i 4500 001 2400419
005 20250522084122.5
006 m o d
007 cr|nu||||||||
008 251215s2024 miu||||||m |||||||eng d
020 $a 9798368482644
035 $a (MiAaPQD)AAI30246128
035 $a AAI30246128
040 $a MiAaPQD $b eng $c MiAaPQD $e rda
100 1 $a Wittig, Andre, $e author. $3 3770400
245 1 0 $a The Mitochondrial ATP Synthase in Cardiac Biology and Disease / $c Andre Wittig.
264 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2024
300 $a 1 electronic resource (140 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertations Abstracts International, Volume: 84-08, Section: B.
500 $a Advisors: Kitsis, Richard N. Committee members: Pessin, Jeffrey.
502 $b Ph.D. $c Albert Einstein College of Medicine $d 2024.
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.
546 $a English
590 $a School code: 2041
650 4 $a Cellular biology. $3 3172791
653 $a Mitochondrial ATP synthase
690 $a 0379
710 2 $a Albert Einstein College of Medicine. $b Biomedical Science. $e degree granting institution. $3 3770386
720 1 $a Kitsis, Richard N. $e degree supervisor.
773 0 $t Dissertations Abstracts International $g 84-08B.
790 $a 2041
791 $a Ph.D.
792 $a 2024
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30246128