Mitochondria Positioning Intrabody Development Service

Creative Biolabs has established Super™ Intrabody Development Platform to offer the most efficient mitochondria-targeting services with a balanced optimization strategy. Through the existed databases of mitochondria matrix residing motif, our scientists can provide multiple specific modifications to meet our clients’ specific requirements.

Mitochondria Positioning

Mitochondria are a double membrane-bound organelle with a common diameter of 0.75-3 µm in all eukaryotic organisms, while are exceptionally absent in red blood cells. Physiologically, mitochondria mainly conduct the energy conversion task to generate most of the cell’s supply of adenosine triphosphate (ATP), and other functions, including:

• Several critical metabolisms such as pyruvate and citric acid cycle.
• Storage of calcium ions and conducting calcium signaling.
• Maintaining control of the cell cycle, cell growth, cell differentiation and apoptosis-programmed cell death, including calcium-evoked apoptosis.
• Signaling through mitochondrial reactive oxygen species.
• Steroid synthesis and hormonal signaling.
• Detoxification of ammonia in the liver.

Generally, the mitochondria could be dissected into several sub-mitochondria structures or compartments as the following:

• Outer membrane: contains porins for free diffusion of small molecules below 5 kDa.
• Intermembrane space or perimitochondrial space: cytochrome c localizes here.
• Inner membrane: performs the redox reactions of oxidative phosphorylation, ATP synthase to generate ATP in the matrix, transport proteins regulate metabolites, and contains cardiolipin, no porins, which is highly impermeable.
• Cristae: numerous cristae studded with small round F₁ particles or oxysomes enhance the ability to produce ATP.
• Matrix: the major function site to oxidate pyruvate and fatty acids and perform citric acid cycle.

Although the mitochondria possess their own genetic material to manufacture RNAs and proteins, more than 98% of the mitochondria proteins are still encoded by the nucleus and synthesized as preproteins in the cytosol. For instance, the human mitochondria genome of 16,569 bp encodes 13 peptides integrated into the inner membrane, meanwhile, 615 distinct types of proteins are identified. As a critical cellular organelle, the mutations or malfunction of mitochondria lead to many disorders, such as Kearns-Sayre syndrome, MELAS syndrome, Leber’s hereditary optic neuropathy, which manifest as myopathy, diabetes, multiple endocrinopathies, etc. Therefore, mitochondria-targeting Abs and other proteins are unceasingly attracting more and more efforts for theoretical research and therapeutic purpose.

Mitochondria-targeting presequences (MTPSs) are usually N-terminal signaling sequences (20-50 amino acids) enriched in positively charged, hydroxylated and hydrophobic residues, which are potential to form amphiphilic α-helices. In the helical wheel projection, the positively charged residues localize to one side of the helix, while the opposite side is uncharged and hydrophobic. Although a consensus sequence for mitochondrial-targeting has not been identified, or maybe there is no such an abstract consensus sequence existed, multiple passenger proteins synthesized as cytosolic precursors with common MTPSs are still directed to localize in mitochondria matrix or other sub-mitochondria structures. During the sorting of proteins targeting mitochondria, the organelle-specific receptors or general import pore (GIP) recognize the MTPSs of precursors escorting by cytosolic chaperones. In particular, these receptors are depicted as follows:

• Translocase of outer membrane
• Translocase of inner membrane

Despite the most extensively studied mitochondrial matrix targeting sequences (MMTSs), a specific combination of MMTS and another signal sequence could direct localization of sub-mitochondrial compartments including the outer membrane, intermembrane space, and inner membrane.

Fig.1 Intrabody scFv (PDB: 5B3N) targeting to mitochondria matrix.

Other Anchoring Modification Options provided by Creative Biolabs

Including the mitochondria, Creative Biolabs can also develop specific positioning antibody for a variety of destination, which including but not limited to:

At Creative Biolabs, our sophisticated platforms are professional to produce intrabody with multiple advance technologies. The subsequent optimization such as positioning characteristic is available to meet our clients’ specific requirements. To learn more details of our specific positioning antibody development platform, please feel free to contact us or direct send us an inquiry.

All of our antibody products and services can only be used for preclinical research studies. Do not use them on humans.