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Mitochondrial liquid-liquid phase separation in Alzheimer's disease

Award Number: R03AG087431
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2025
PERIOD OF PERFORMANCE END DATE: 06/14/2026

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Mitochondrial liquid-liquid phase separation in Alzheimer's disease - PROJECT SUMMARY In Alzheimer's disease, abnormalities in the morphology, transport, and functions of mitochondria are prevalent. Mitochondria are cellular organelles that generate energy to fuel cellular metabolism. Toxic Aβ42 is known to concentrate in mitochondria. However, how Aβ42 affects crucial mitochondrial processes that maintain mitochondrial health is still unclear. The long-term objective is to contribute to developing mechanism- based treatment strategies for Alzheimer's disease. The overarching goal of this application is to identify the mechanisms responsible for Aβ42's effects on the regulation of mitochondrial gene expression after transcription and mitochondrial dysfunction in a basic cell model. The central hypothesis is that Aβ42 interferes with mitochondrial liquid-liquid phase separation, causing morphological and functional mitochondrial defects in Alzheimer's disease. The rationale for the proposed research is that a mechanism-based determination of Aβ42's role in mitochondrial dysfunction will provide new opportunities for developing novel strategies to intervene in Alzheimer's disease. To attain the overall objective, the following two specific aims will be pursued: (Aim 1) Investigate the impact of Aβ42 on mitochondrial ribonucleoprotein granule dynamics in mitochondria.; (Aim 2) Optogenetic control of Aβ42 and mitochondrial ribonucleoprotein granules in mitochondria. At the completion of these aims, this project will provide insights into how to maintain mitochondrial health by modulating the mitochondrial liquid-liquid phase separation in Alzheimer's disease.


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	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Aging Research	002	1	9/15/2026	NEW	$0
2026	2025	YESHIVA UNIVERSITY	500 W 185TH ST	NEW YORK	NY	10033	NEW YORK	USA	Aging Research	001	2	8/17/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$151,475
2026	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Aging Research	000	1	8/7/2026	NEW	-$151,475
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $308,000 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Aging Research	000	1	12/13/2024	NEW	$310,000
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Aging Research	001	1	12/18/2024	NEW	-$2,000
														Subtotal = $308,000

Grand Total All Awards = $308,000

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Mitochondrial liquid-liquid phase separation in Alzheimer's disease

Award Number: R03AG087431

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2025

PERIOD OF PERFORMANCE END DATE: 06/14/2026

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