A mitochondrion has multiple copies of its DNA and a typical cell has many mitochondria . As a result, cells usually have many copies – often thousands of mitochondrial DNA. Mitochondria DNA are randomly distributed to daughter cells during mitosis and meiosis.

The mitochondrial genome is distinct from the nuclear genome .The Mitochondrial DNA  contain genes that encodes 22 transfer RNAs, 13 messenger RNAs, and 2 ribosomal RNAs. Although mitochondrial genes encode some messenger RNA that will be translated to protein, these organelles require nuclear encoded genes to perform their function.

Dr.V.Malathi

Associate Professor

Department of Biochemistry

Ethiraj College for Women

Chennai-6000 08

Tamil Nadu

India.

As mitochondria are inherited from a person's mother, they help to trace matrilineal ancestry.

Mitochondrial DNA mutations are often deletions or point mutations. In general  1 in 400 person has a maternally inherited pathogenic mitochondrial DNA mutation . In individual families ,it is difficult to distinguish whether mitochondrial inheritance is from autosomal dominant or from  X-linked inheritance, but however , the sex of the transmitting and non transmitting parents can suggest a mitochondrial basis

A nuclear gene, called DNA polymerase gamma ( POL G) encodes the DNA polymerase responsible for replicating the mitochondrial genome. The POLG protein consists of two domains: a catalytic domain that exhibits polymerase activity, and an exonuclease domain that is involved in the recognition and removal of DNA base pair mismatches that occur during DNA replication. A recent study suggests that mitochondria may have a nucleotide imbalance that leads to decreased POLG fidelity and higher mitochondrial DNA mutation rates .

Mutations in mitochondrial DNA can lead to human genetic disorders.

Image from "Mitochondrial," by the National Institutes of Health (public domain).

The first human disease that was associated with a mutation in mitochondrial DNA is called Leber's Hereditary Optic Neuropathy, or LHON.  LHON causes a painless loss of central vision between 12 and 30 years of age. Both eyes are affected at the same time.

Large deletions in mitochondrial DNA cause a condition called Kearns-Sayre Syndrome. These deletions affect the mitochondria from doing their job of extracting energy. Kearns-Sayre Syndrome can cause symptoms such as weakness of the muscles, including those that control eyelid and eye movement, as well as degeneration of the retina and development of heart disease

Leigh syndrome is a rare inherited neurometabolic disorder that affects the central nervous system (brain, spinal cord, and optic nerve). This disorder begins in infants between the ages of 3 months and 2 years . Rarely, it can occur in teenagers and adults. Mutations in mitochondrial DNA (mtDNA) and over 30 genes in nuclear DNA have been implicated in Leigh disease. The most common of these mutations (in 10 to 20 percent of Leigh syndrome ) occurs in MT-ATP6. This gene codes for ATP synthase, an enzyme that directly generates ATP present in the last complex of the oxidative  phosphorylation chain. The most common MT-ATP6 mutation found with Leigh syndrome is a point mutation occurring  at nucleotide 8993. This mutation changes a thymine to a guanine

• In case of suspected mitochondrial disease , Next generation sequencing with gene dosage of nuclear DNA (n DNA ) and mitochondrial DNA (mt DNA) from blood or urine sediment  or affected tissues like muscle , buccal swab, liver etc., can be done .
• Mutations, rearrangements, or deletions that are tissue specific are identified  by Tissue-based testing
•  Genetic consultation/ counselling  is also advised.

• Evaluation of selected mitochondrial biomarkers in blood, urine, and spinal fluid such as the measurements of lactate and pyruvate in plasma and cerebrospinal fluid (CSF), plasma, urine, and CSF amino acids, plasma acyl carnitines, and urine organic acids.
• Lactate elevation occurs because the flux through glycolysis overwhelms the utilization of pyruvate in the mitochondria. Elevated plasma lactate (>3 mmol/l), in a properly collected sample, suggests the presence of mitochondrial dysfunction. This can be due either to primary mitochondrial disease or, secondarily, to organic acidemias, other inborn errors of metabolism, toxins, tissue ischemia, and certain other diseases.
• In patients with associated neurologic symptoms, elevated CSF lactate can be a helpful marker of mitochondrial disease .
• Quantitative amino acid analysis like  alanine, glycine, proline, and threonine in blood or spinal fluid is commonly obtained when evaluating a patient with possible mitochondrial disease. This occurs due to the altered redox state created by respiratory chain dysfunction including alanine, glycine, proline, and threonine

• Structural alterations in neuroimaging like computed tomography and magnetic resonance imaging of the brain have been used in the diagnosis of mitochondrial disorders, depending on the type of mitochondrial disorder and type of central nervous system involvement.

       Exercise - including both endurance exercises (walking, running, swimming, dancing, cyclin etc.,)  and resistance/strength training (sit-ups, arm curls, knee extensions, weight lifting etc.,). These are done to increase muscle size and strength

       Vitamin or amino acid supplements- Coenzyme Q10; B complex vitamins, especially thiamine (B1) and riboflavin (B2) ;Alpha lipoic acid; L-carnitine ; Creatine ; and L-Arginine.

• Mitochondrial replacement therapies (MRT) in oocytes or zygotes such as pronuclear (PNT), spindle (ST) or polar body (PBT) transfer could prevent second generation transmission of mitochondrial DNA (mtDNA) defects.
• Preimplantation genetic diagnosis (PGD) is an IVF-based reproductive option.  PGD is suitable for some women with mtDNA disease who wish to conceive a genetically related child with a reduced risk of severe disease. The procedure involves the in vitro fertilization of oocytes harbouring pathogenic mtDNA mutations. These are either cultured and subjected to mutation  analysis. PGD allows specialists to provide a better prognosis of disease
• Mitochondrial Donation (MD) is a reproductive option . The procedure involves removing the nuclear DNA from an oocyte or zygote containing mutated mt DNA and transferring this to an enucleated oocyte or zygote that contains WT mt DNA from a healthy donor.
• Pronuclear transfer (PNT) involves removal of the pronuclei in a membrane-bound karyoplast from a fertilized zygote and transfer to an enucleated donor zygote.

Reviewer : Mr. Rajmohan Govindaswamy , CEO, Cogniti Digital Solutions ,Chennai, Tamil Nadu, India

The book provides an in-depth exploration of the phenomenon of mitochondrial inheritance, which is the transmission of genetic material from the mitochondria of a mother to her  offspring. The author covers a range of topics related to mitochondrial inheritance, including the history of research in this area, the genetic mechanisms involved, and the implications for human health and disease.

The book is aimed at a general audience, including students, researchers, and healthcare professionals, and is presented in a clear and accessible style. Dr.Malathi Veeramani has well    illustrated the concepts discussed, and provides a wealth of information and insights into this fascinating and complex field of study.

Overall, "Mitochondrial Inheritance" is a valuable resource for anyone interested in genetics, inheritance, and human health, and provides a comprehensive overview of this important area of research.

Reviewer : Dr. Kothandharaman Subramaniam, Researcher , Senior Research Scientist, Sing Health, Singapore

Hi Malathi. I went through chapters of your book on Mitochondria. It's very well written, as the flow is very simple and easy to follow, especially for students. Fantastic effort by you. Keep up your good work. ??????

Reviewer : Dr.R.Venkateswari , Assistant professor , Department of Medical Biochemistry, University of Madras, Chennai, Tamil Nadu, India

Dear Dr.Malathi, it is very interesting to read your open text book on mitochondrial inheritance. You have given all the points in a crisp manner under suitable subheadings. It is very   interesting to know about the mitochondrial inheritance and gene mutations leading to the disorders. Thank you for giving me an opportunity to review your book.

Reviewer : Dr. G.Gopal, Associate Professor , Department of Molecular Oncology, Cancer Institute, Adayar, Chennai, Tamil Nadu, India 

Mitochondrial inheritance ,  book written by Dr. V. Malathi is very informative and provides necessary basic information on mitochondrial DNA, mitochondrial DNA mutations and      disease and the treatment options available. The book serves as an introduction to students who wish to learn more about the biology of mitochondria. Mitochondrial alterations are  being intensively studied and present several opportunities to perform research. Our lab has been studying mito ribosomal proteins and their role in cancer and I would definitely            recommend research scholars to access this book for a quick overview of mitochondrial inheritance.

Mitochondria are unique cellular organelles  in having a DNA of their own. This mitochondrial DNA is known as mtDNA . In nearly all mammals the mitochondrial DNA is exclusively     inherited from the mother and fathers also occasionally contribute to the inheritance. mt DNA mutations accumulate during human life and may contribute a wide range of pathologies. Thus understanding how mt DNA is inherited has wide implications across medicine .

This project is aimed at creating an open textbook for the global student community. This open textbook attempts to unravel the basic concepts about mitochondrial DNA , its                inheritance and mitochondrial genetic disorders . The book also features with interactive exercises .

Very similar to Print My Blog Quick Print, but supporting Pro features. Great for making a PDF for an easy-to-read digital backup of your favorite website content.

Features

• Supports nesting articles (like posts and pages) into “parts”
• External hyperlinks (links to web pages not in the project) can be automatically converted to footnotes, left in-place, or removed
• Internal hyperlinks (links to content included in the project) can be automatically converted to to footnotes, inline page references, left in-place, or removed
• The default title page can include: Project Title, Subtitle, Site URL, Date Printed, Credit to Print My Blog
• Each article can include: Title, ID, Author, URL, Date Published, Categories and Tags, Featured Image, Excerpt, Custom Fields, Content
• Limit image size by setting maximum height
• Optionally automatically center images
• Optionally float images to the top or bottom of each page

Page Layout

• Page numbers in bottom-right corner, article titles in the top-right, and part titles (if using parts) appear in the top-left corner. Front-matter’s pages are numbered with Roman numerals
• Each article can optionally begin on a new page

Perfect for editing and reviewing your content! Compact to conserve paper, lots of meta-information, and double-spaced text to allow for editor’s notes.

Features

• Supports nesting articles (like posts and pages) into “parts”
• External hyperlinks (links to web pages not in the project) can be automatically converted to footnotes or removed
• Internal hyperlinks (links to content included in the project) can be automatically converted to footnotes, inline page references, or removed
• The default title page can include: Project Title, Subtitle, Site URL, Date Printed, Credit to Print My Blog
• Each article can include: Title, ID, Author, URL, Date Published, Categories and Tags, Featured Image, Excerpt, Custom Fields, Content
• Optionally automatically center images
• Optionally float images to the top or bottom of each page

Page Layout

This design is meant for printing on both sides of the page so you see two pages at once (the "page spread"). So the left-hand page will be styled differently than the right-hand page.

• Page numbers in bottom-outside corner, part titles appear in the top of the left page, article titles appear at the top of the right page. Front-matter’s pages are numbered with Roman numerals
• Each article can optionally begin on a new page

Very similar to Print My Blog Quick Print, but supporting Pro features. Great for printing your WordPress content.

Features

• Supports nesting articles (like posts and pages) into “parts”
• External hyperlinks (links to web pages not in the project) can be automatically converted to footnotes or removed
• Internal hyperlinks (links to content included in the project) can be automatically converted to footnotes, inline page references, or removed
• The default title page can include: Project Title, Subtitle, Site URL, Date Printed, Credit to Print My Blog
• Each article can include: Title, ID, Author, URL, Date Published, Categories and Tags, Featured Image, Excerpt, Custom Fields, Content
• Optionally automatically center images
• Optionally float images to the top or bottom of each page

Page Layout

This design is meant for printing on both sides of the page so you see two pages at once (the "page spread"). So the left-hand page will be styled differently than the right-hand page.

• Page numbers in bottom-outside corner, part titles appear in the top of the left page, article titles appear at the top of the right page. Front-matter’s pages are numbered with Roman numerals
• Each article can optionally begin on a new page

For creating a printout of your WordPress content that saves paper and ink.

This design uses a smaller font, small images, doesn’t add pagebreaks between articles, and avoids unnecessary extra information.

Features

• Supports nesting articles (like posts and pages) into “parts”
• External hyperlinks (links to web pages not in the project) can be automatically converted to footnotes or removed
• Internal hyperlinks (links to content included in the project) can be automatically converted to footnotes, inline page references, or removed
• The default title page can include: Project Title, Subtitle, Site URL, Date Printed, Credit to Print My Blog
• Each article can include: Title, ID, Author, URL, Date Published, Categories and Tags, Featured Image, Excerpt, Custom Fields, Content
• Optionally automatically center images
• Optionally float images to the top or bottom of each page

Page Layout

This design is meant for printing on both sides of the page so you see two pages at once (the "page spread"). So the left-hand page will be styled differently than the right-hand page.

• Page numbers in bottom-outside corner, part titles appear in the top of the left page, article titles appear at the top of the right page. Front-matter’s pages are numbered with Roman numerals
• Each article can optionally begin on a new page

Designed for a school, company, or organization that wants to include their name, logo, and colors throughout the PDF. Because of its exstensive use of colors, it’s usually best viewed from a computer or handheld device.

Features

• Easier content editing because there are no nesting parts.
• All hyperlinks converted into footnotes
• The title page can include your organization’s name, project title, issue number, list of authors, and an introductory paragraph.
• Each article includes just its title and content

Page Layout

• The default title page includes a stylized banner (with customizable color) above a colored background featuring a large version of your company logo.
• Main matter pages fade from white to a color of your choosing in the corner where your logo and page number are shown.
• Page numbers in bottom-right corner, and article titles in the top-right. Front-matter’s pages are numbered with Roman numerals
• Each article begins on a new page
• Back matter uses your large company logo with background color

Designed to look good when viewed from a device or printing to paper. The two-column layout leads to more compact content, especially good if your content doesn’t require the full page width

Features

• Main matter is divided into two columns, while front matter uses the full page width.
• Content can be divided into parts with a special part opening area using the full page width.
• The title page can include a title and preamble. Other content can immediately follow, without needing a page break.
• Each article includes just its title and content, and an optional dividing line to help distinguish between articles.
• If your content is already divided into columns, optionally automatically remove them to improve the layout.
• Optionally begin each post on a new page, or be shown immediately following the previous one.
• Optionally have each article title take up the full page width, or show them inside columns.
• Internal links (hyperlinks to content included in the project) are replaced with page references.
• External links (hyperlinks to content on the internet) are left as-is.

Page Layout

• Most content is divided between two columns.
• Page numbers in bottom-right corner, and part titles in the top-left. Front-matter’s pages are numbered with Roman numerals

Special Instructions

Front matter defaults to using the full page width. To force something to be divided into columns, add the CSS class "mayer-columns" inside your content.

Main matter defaults to being divided into columns. To force something to use the full page width, add the CSS class "mayer-wide" inside the content.

Similar to Print My Blog Quick Print and dotEpub, but supporting Pro features. Great for printing your WordPress content as an eBook for reading from a tablet or phone, or uploading to eBook marketplaces like Amazon or Apple Book Store.

A table of contents is generated and inserted into the book (no need to add it using an external service like Kindle Direct Publishing or Calibre).

Images are bundled into the book file so they can be used offline.

Image galleries are rearranged into a simple list of images which displays better on smaller devices.

If there are any features or options you want, please get in touch.

Features

• Supports nesting articles (like posts and pages) into “parts”
• External hyperlinks (links to web pages not in the project) are left as working hyperlinks
• Internal hyperlinks (links to content included in the project) are converted into links to the appropriate page of the eBook
• The default title page can include: Project Title, Subtitle, Site URL, Date Printed, Credit to Print My Blog
• Each article can include: Title, ID, Author, URL, Date Published, Categories and Tags, Featured Image, Excerpt, Custom Fields, Content
• All images are automatically included in the ePub file (instead of merely pointing to the external image source). This makes the filesize larger, but allows users to view images while disconnected from the Internet.
• Small images are automatically centered
• Image galleries are converted into regular list of images, which look better on small screens.

Page Layout

The page design is mostly dictated by the app and device used for reading

Each article begins on a new page.

Similar to Print My Blog Quick Print's other "Classic" designs, except optimized for reading by Microsoft Word. Useful when you need to deliver your content as a Microsoft Word Document (like to an editor), or for using as an intermediate format for delivery to other applications (like for importing into Adobe InDesign).

A table of contents is generated and inserted at the requested location. Once in Microsoft Word, right click on the table of contents and click "Update Field"; or press Ctrl + A, then F9.

Images may be bundled into the Word Document file so they can be used offline or if the website hosting the images goes offline.

Image galleries are rearranged into a simple list of images which displays better on smaller devices.

If there are any features or options you want, please get in touch.

Features

• Supports nesting articles (like posts and pages) into “parts”
• External hyperlinks (links to web pages not in the project) may be left as working hyperlinks or removed
• Internal hyperlinks (links to content included in the project) may be converted into links to the appropriate page of the document, left as hyperlinks to the website, or removed.
• The default title page can include: Project Title, Subtitle, Site URL, Date Printed, Credit to Print My Blog
• Each article can include: Title, ID, Author, URL, Date Published, Categories and Tags, Featured Image, Excerpt, Custom Fields, Content
• All images are automatically included in the Word Document file (instead of merely pointing to the external image source). This makes the filesize larger, but allows users to view images while disconnected from the Internet.
• Small images are automatically centered
• Image galleries are converted into regular list of images, which look better on small screens.

Page Layout

Each article begins on a new page.

Multi-column newspaper design designed for printing. Wide images can span multiple columns and always snap to the nearest page edge to make a visually-appealing layout.

Features

• The "Title page" is actually a special header on the front page containing your publication's title, issue number, date, and other optional prominent info (set on the design and project meta settings).
• Content is divided into two, three, or four columns.
• The top margin contains the front page (publication title, issue number, date, etc.).
• Designed for duplex printing with the left page mirroring the right page's margins.
• Content can be divided into parts. Part openings and important articles' titles and cover images take up the full page width, whereas regular articles compactly fit into columns.
• Each article may include post title, ID, author, published date, categories and tags, URL, featured image, excerpt, custom fields, and content.
• If your content is already divided into columns, optionally automatically remove them to improve the layout.
• External hyperlinks (links to web pages not in the project) can be automatically converted to footnotes or removed
• Internal hyperlinks (links to content included in the project) can be automatically converted to footnotes, inline page references, or removed

Page Layout

• Issue and page number are in the outside top margin, the publication's title is in the middle top margin, and the publication date is in the inside top margin. The optional publication subtitle is underneath the other top-margin content.

Section Templates

Choose different styles for articles included in your project:

• Default Template: shows all content specified by the "Post Content" design setting (e.g. the article's title and featured image) in columns.
• Single Column: like the default template, but in a single column.
• Fullpage Content: contains only the article's content (no title, featured image, etc.) all in a single, wide column.
• Full Column Content: like "Fullpage Content", except content is still divided into multiple columns..
• Important: shows the article's featured image and title across all columns, but other content is shown in multiple columns.

Parts start on a new page and include the part’s title, featured image, and content.

Special Instructions

Note that in order to improve page layout, all images and figures snap to the nearest page edge.

"Full width" images take up all columns and snap to the nearest page edge.

"Wide width" images take up 2 columns and snap to the nearest page edge.

Add the CSS class "pmb-dont-snap" to any images you don't want to snap like this.