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BIOGENESIS OF THE MITOCHONDRIAL INNER MEMBRANE

Award Number: R01GM061721
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2000
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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BIOGENESIS OF THE MITOCHONDRIAL INNER MEMBRANE - SUMMARY Mitochondrial dysfunction is a common contributing factor to degenerative diseases, including the neural and muscular systems; yet mechanistic studies in mammals are limited because adequate tools and approaches are lacking. Moreover, a greater understanding of the protein translocation mechanisms in model organisms such as S. cerevisiae and zebrafish is needed, because protein translocation is linked to metabolism, signaling, and mitochondrial quality control and stress pathways such as mitophagy. Long-term, modulating mitochondrial protein import pathways therefore is a potential target for treating diseases. The overall goals of this proposal are (1) to increase our mechanistic understanding of protein import pathways into mitochondria in both yeast and mammalian cells and (2) to understand how defects in protein translocation contribute to disease. Attenuating protein translocation pathways can alter the location of mitochondrial proteins that are dual-localized (located to mitochondria and another compartment), change mitochondrial stress pathways, and induce selective turnover of mitochondria via mitophagy. However, there is a critical gap in developing small molecule probes with specificity for modulating mitochondrial protein import specifically in mammalian cells while minimizing off-target effects. Three specific study aims are proposed to accomplish these goals. In Aim 1, a new cell based screen in mammalian cells to identify modulators for all mitochondrial protein import pathways and specific cargo will be implemented. In Aim 2, a series of experimental approaches will be used to characterize specificity of the probes, to minimize off-target effects in mammalian cells and yeast, with the goal of developing specific probes. In Aim 3, existing and new small molecules will be characterized in mechanistic studies, particularly focusing on how defects in protein import alter mitochondrial stress pathways in mitophagy. In addition to increasing fundamental knowledge about the mechanisms of protein translocation in mitochondria, this application may have a broad impact on public health because our approach will provide new tools that will provide a strategy for developing therapeutics for diseases that can be modified by attenuating protein translocation.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	21	12/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $429,221 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	21	8/7/2025	NON-COMPETING CONTINUATION	$429,221
														Subtotal = $429,221

Issue Date FY: 2024 ( Subtotal = $429,221 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	20	9/10/2024	NON-COMPETING CONTINUATION	$429,221
														Subtotal = $429,221

Issue Date FY: 2023 ( Subtotal = $810,367 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	003	19	7/24/2023	SUPPLEMENT FOR EXPANSION	$10,789
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	002	19	7/19/2023	SUPPLEMENT FOR EXPANSION	$332,594
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	18	2/23/2023	SUPPLEMENT FOR EXPANSION	$37,763
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	19	7/18/2023	NON-COMPETING CONTINUATION	$429,221
														Subtotal = $810,367

Issue Date FY: 2022 ( Subtotal = $353,309 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	18	7/27/2022	COMPETING CONTINUATION	$429,221
2022	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	17	3/1/2022	NON-COMPETING CONTINUATION	-$75,912
														Subtotal = $353,309

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	17	8/24/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $414,285 )
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	17	7/27/2018	NON-COMPETING CONTINUATION	$414,285
														Subtotal = $414,285

Issue Date FY: 2017 ( Subtotal = $414,285 )
2017	2017	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	16	7/24/2017	NON-COMPETING CONTINUATION	$414,285
														Subtotal = $414,285

Issue Date FY: 2016 ( Subtotal = $414,285 )
2016	2016	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	15	8/9/2016	NON-COMPETING CONTINUATION	$414,285
														Subtotal = $414,285

Issue Date FY: 2015 ( Subtotal = $459,727 )
2015	2015	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	14	8/28/2015	COMPETING CONTINUATION	$459,727
														Subtotal = $459,727

Issue Date FY: 2013 ( Subtotal = $364,493 )
2013	2013	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	13	8/29/2013	NON-COMPETING CONTINUATION	$364,493
														Subtotal = $364,493

Issue Date FY: 2012 ( Subtotal = $377,716 )
2012	2012	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	12	9/6/2012	NON-COMPETING CONTINUATION	$377,716
														Subtotal = $377,716

Issue Date FY: 2011 ( Subtotal = $377,720 )
2011	2011	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	11	9/1/2011	NON-COMPETING CONTINUATION	$377,720
														Subtotal = $377,720

Issue Date FY: 2010 ( Subtotal = $401,486 )
2010	2010	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	001	10	8/31/2010	COMPETING CONTINUATION	$401,486
2010	2009	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	9	8/30/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $401,486

Issue Date FY: 2009 ( Subtotal = $338,303 )
2009	2009	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	9	4/16/2009	NON-COMPETING CONTINUATION	$338,303
														Subtotal = $338,303

Issue Date FY: 2008 ( Subtotal = $328,450 )
2008	2008	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Biomedical Research and Research Training	000	8	4/25/2008	NON-COMPETING CONTINUATION	$328,450
														Subtotal = $328,450

Issue Date FY: 2007 ( Subtotal = $328,409 )
2007	2007	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	10920 WILSHIRE BLVD, 5TH FLOOR	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	7	5/18/2007	NON-COMPETING CONTINUATION	$328,409
														Subtotal = $328,409

Issue Date FY: 2006 ( Subtotal = $343,011 )
2006	2006	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	10920 WILSHIRE BLVD, 5TH FLOOR	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	6	3/31/2006	COMPETING CONTINUATION	$328,363
2006	2006	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	10920 WILSHIRE BLVD, 5TH FLOOR	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	6	9/21/2006	SUPPLEMENT FOR EXPANSION	$14,648
														Subtotal = $343,011

Issue Date FY: 2004 ( Subtotal = $260,304 )
2004	2004	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	10920 WILSHIRE BLVD, 5TH FLOOR	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	000	5	8/30/2004	NON-COMPETING CONTINUATION	$260,304
														Subtotal = $260,304

Issue Date FY: 2003 ( Subtotal = $379,319 )
2003	2003	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	10920 WILSHIRE BLVD, 5TH FLOOR	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cell Biology and Biophysics Research	001	4	9/19/2003	SUPPLEMENT FOR EXPANSION	$119,015
2003	2003	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	10920 WILSHIRE BLVD, 5TH FLOOR	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cell Biology and Biophysics Research	000	4	8/29/2003	NON-COMPETING CONTINUATION	$260,304
														Subtotal = $379,319

Issue Date FY: 2002 ( Subtotal = $313,940 )
2002	2002	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	10920 WILSHIRE BLVD, 5TH FLOOR	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cell Biology and Biophysics Research	001	2	7/1/2002	SUPPLEMENT FOR EXPANSION	$7,477
2002	2002	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	10920 WILSHIRE BLVD, 5TH FLOOR	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cell Biology and Biophysics Research	000	3	9/2/2002	NON-COMPETING CONTINUATION	$306,463
														Subtotal = $313,940

Grand Total All Awards = $8,084,185

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BIOGENESIS OF THE MITOCHONDRIAL INNER MEMBRANE

Award Number: R01GM061721

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2000

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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