Mitochondrial Membrane Permeability Transition Pore Research Service

Introduction Services Measurements Advantages Inquiry Workflow FAQs Published Data

Creative Biolabs offers comprehensive mitochondrial membrane permeability transition pore research services, investigating the molecular mechanisms by which mPTP modulation influences skin health and aging. Our research supports the formulation of cosmetics designed to enhance mitochondrial function and combat the visible signs of aging.

Introduction

The mitochondrial membrane permeability transition pore (mPTP) is a vital component of mitochondrial function, responsible for regulating the permeability of the inner mitochondrial membrane under stress conditions. When the mPTP opens abnormally, it leads to mitochondrial dysfunction, oxidative stress, and cellular damage, processes that contribute to aging and degenerative diseases. In skin cells, mitochondrial dysfunction is a key factor in the development of visible signs of aging, such as wrinkles, sagging, and reduced skin elasticity. As cells age, their mitochondria become less efficient, producing less ATP and increasing the production of reactive oxygen species (ROS). This imbalance triggers a cascade of events that degrade collagen and elastin fibers, leading to skin aging. The mPTP plays a critical role in this process, as its opening leads to further mitochondrial damage, exacerbating oxidative stress and inflammation.

Fig.1 A picture of the latest structural models of the MPTP. (OA Literature) Fig. 1 One of the latest structural models of the MPTP (ATP synthasome) and important factors regulating its functional state.¹

Services

Our mitochondrial membrane permeability transition pore (mPTP) research focuses on understanding how various compounds influence mitochondrial function in skin cells. We employ advanced methods like fluorescence microscopy to visualize changes in mitochondrial membrane potential and permeability. Additionally, we use biochemical assays to measure the release of cytochrome c and mitochondrial swelling, both of which indicate mPTP opening. The significance of our research lies in its ability to uncover novel insights into the molecular mechanisms driving skin aging, oxidative stress, and inflammation. By understanding how mPTP modulates these processes, we can develop more effective skincare formulations aimed at enhancing mitochondrial function, improving skin rejuvenation, and mitigating age-related changes at the cellular level. Our research is designed to help guide the development of targeted anti-aging products, offering a detailed mechanistic approach to assessing their efficacy.

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Measurements

We offer a comprehensive suite of advanced measurements to assess mitochondrial dysfunction and mPTP activity, utilizing state-of-the-art technologies to provide detailed insights into mitochondrial health. Our evaluations include, but are not limited to:

General Observations: Mitochondrial membrane potential (Δψm), mPTP opening, and mitochondrial swelling assays.
Mitochondrial Permeability Transition: Detection of mPTP opening through cytochrome c release assays and mitochondrial swelling tests.
Mitochondrial Bioenergetics: Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) measurements to assess mitochondrial function, using Seahorse XF technology.
Immunohistochemistry: Detection of mitochondrial markers (e.g., TOM20, COX IV) to evaluate mitochondrial distribution and integrity in skin tissue samples.
Cellular Viability & ROS Generation: Cell viability assays (MTT, CCK-8) and reactive oxygen species (ROS) generation assays to quantify oxidative stress induced by mPTP opening.
Gene/Protein Expression Profiling: RT-qPCR and Western blotting for the expression of mitochondrial proteins involved in mPTP regulation (e.g., Cyclophilin D, Bax, Bcl-2).

In addition to our established models of mPTP research, we offer customized experimental designs, including the development of specific cell-based and animal models for evaluating the effects of cosmetic formulations on mPTP dynamics.

Advantages

1. Comprehensive Service Offering: Our services span the full spectrum of mPTP research, including gene/protein expression analysis, cellular viability assays, ROS generation studies, and mitochondrial dynamics evaluations. We ensure that all aspects of mitochondrial health are thoroughly investigated.

2. Advanced Models and Personalized Approach: We develop both established and novel cell-based and animal models to study mPTP function in the context of skin aging. Our team works closely with clients to select the best models and offer support in experimental design and data interpretation.

3. Proven Track Record: Our research has contributed to the development of effective anti-aging products, providing clients with data-backed evidence to support product efficacy and claims. We have a history of successful collaborations with top cosmetic and pharmaceutical companies.

4. Flexible and Efficient Process: We understand the need for timely results and offer efficient project management. Our streamlined processes allow for rapid turnaround times without compromising on the quality or depth of the research.

5. Dedicated Scientific Support: Our scientific team is available at every stage of your project, from initial consultation to final analysis. We provide clear, actionable insights and are committed to delivering exceptional support throughout your research journey.

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Workflow

Fig 3. Workflow of Creative Biolabs service. (Creative Biolabs Original)

FAQs

What is the role of the mitochondrial membrane permeability transition pore in skin aging?

The mPTP regulates the permeability of the mitochondrial membrane and is implicated in oxidative stress, apoptosis, and inflammation. These processes contribute to the visible signs of aging, such as wrinkles and reduced skin elasticity.

How does mPTP research contribute to anti-aging cosmetic development?

By studying how compounds affect mPTP opening and mitochondrial function, we can design cosmetic formulations that support mitochondrial health, reduce oxidative damage, and promote skin rejuvenation.

What methods are used to assess mPTP activity?

We use a combination of biochemical assays, fluorescence microscopy, and bioenergetic measurements to assess mPTP activity and its impact on mitochondrial function.

Can you customize research to focus on specific ingredients?

Yes, we offer tailored research services to assess the effects of specific ingredients on mitochondrial function and mPTP activity, allowing for detailed insights into their anti-aging potential.

How long does it take to complete a typical mPTP study?

The timeline for mPTP research varies depending on the complexity of the project, but typical studies range from 4 to 8 weeks for initial results.

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Published Data

Fig.2 Phosphate depletion increases mitochondrial membrane potential through the ADP/ATP carrier in cells lacking the electron transport chain (ETC) and ATP synthase. (OA Literature) Fig. 2 Loss of OSCP/atp-3 during adulthood selectively recapitulates mitochondrial permeability transition pore (mPTP)-like characteristics.²

The assembly of respiratory complexes was examined to identify additional factors related to the electron transport chain (ETC) and ATP synthase that contribute to mitochondrial membrane potential (MMP). Using BN-PAGE, it was observed that in wild-type cells, phosphate depletion led to a modest increase in the abundance of ETC complexes compared to cells grown under normal phosphate conditions (Figure A). Treatment with bongkrekic acid in wild-type cells significantly reduced the phosphate depletion-induced enhancement of MMP (Figure B). Furthermore, a combination of antimycin A and bongkrekic acid treatment completely blocked the increase in MMP triggered by low phosphate levels (Figure B). To further investigate this, rho⁰ cells, which lack complex III, complex IV, and a complete ATP synthase, were grown under both low and high phosphate conditions. These cells showed a phosphate depletion-induced increase in MMP, which was completely abolished by bongkrekic acid in a dose-dependent manner (Figure C). The findings suggest that phosphate depletion enhances MMP through a mechanism independent of the ETC and ATP synthase. Specifically, the ADP/ATP carrier, by importing ATP^4- and exporting ADP^3-, facilitates a net export of positive charges from the matrix to the intermembrane space (IMS) (Figure D).

References

Endlicher, René et al. "The Mitochondrial Permeability Transition Pore-Current Knowledge of Its Structure, Function, and Regulation, and Optimized Methods for Evaluating Its Functional State." Cells vol. 12,9 1273. 27 Apr. 2023, DOI:10.3390/cells12091273. Distributed under Open Access license CC BY 4.0, without modification.
Ouyang, Yeyun et al. "Phosphate starvation signaling increases mitochondrial membrane potential through respiration-independent mechanisms." eLife vol. 13 e84282. 22 Jan. 2024, DOI:10.7554/eLife.84282. Distributed under Open Access license CC BY 4.0, without modification.