- Title
- Functional interactions between complex I and complex II with nNOS in regulating cardiac mitochondrial activity in sham and hypertensive rat hearts
- Creator
- Wu, Yu N; Sudarshan, Vidya K.; Zhu, Shi Chao; Shao, Yong Feng; Kim, Sung Joon; Zhang, Yin Hua
- Relation
- Pflugers Archiv Vol. 472, Issue 12, p. 1743-1755
- Publisher Link
- http://dx.doi.org/10.1007/s00424-020-02458-2
- Publisher
- Springer
- Resource Type
- journal article
- Date
- 2020
- Description
- Nitric oxide (NO) affects mitochondrial activity through its interactions with complexes. Here, we investigated regulations of complex I (C-I) and complex II (C-II) by neuronal NO synthase (nNOS) in the presence of fatty acid supplementation and the impact on left ventricular (LV) mitochondrial activity from sham and angiotensin II (Ang-II)–induced hypertensive (HTN) rats. Our results showed that nNOS protein was expressed in sham and HTN LV mitochondrial enriched fraction. In sham, oxygen consumption rate (OCR) and intracellular ATP were increased by palmitic acid (PA) or palmitoyl-carnitine (PC). nNOS inhibitor, S-methyl-l-thiocitrulline (SMTC), did not affect OCR or cellular ATP increment by PA or PC. However, SMTC increased OCR with PA + malonate (a C-II inhibitor), but not with PA + rotenone (a C-I inhibitor), indicating that nNOS attenuates C-I with fatty acid supplementation. Indeed, SMTC increased C-I activity but not that of C-II. Conversely, nNOS-derived NO was increased by rotenone + PA in LV myocytes. In HTN, PC increased the activity of C-I but reduced that of C-II, consequently OCR was reduced. SMTC increased both C-I and C-II activities with PC, resulted in OCR enhancement in the mitochondria. Notably, SMTC increased OCR only with rotenone, suggesting that nNOS modulates C-II-mediated OCR in HTN. nNOS-derived NO was partially reduced by malonate + PA. Taken together, nNOS attenuates C-I-mediated mitochondrial OCR in the presence of fatty acid in sham and C-I modulates nNOS activity. In HTN, nNOS attenuates C-I and C-II activities whereas interactions between nNOS and C-II maintain mitochondrial activity.
- Subject
- nNOS; heart; mitochondria; momplex i; hypertension
- Identifier
- http://hdl.handle.net/1959.13/1441431
- Identifier
- uon:41423
- Identifier
- ISSN:0031-6768
- Language
- eng
- Reviewed
- Hits: 1774
- Visitors: 1773
- Downloads: 0