Mitochondrial Fatty Acid Transport System and its
Relevance to Ovarian Function
Mona Sharma
Department of Reproductive Biology, All India Institute of Medical Sciences, New Delhi-110029, India
Received: 06/12/2017
Accepted: 1/03/2018
Published: 20/03/2018
Abstract
Mitochondrial fatty acid oxidation is integral to folliculogenesis and oocyte maturation. Mitochondrial fatty acid transport system
includes molecules such as 3-hydroxy-4-trimethylamino butyrate or carnitine, organic cation transporter novel 2 (OCTN2), carnitine
palmitoyl transferase (CPT1), CPT2, and carnitine-acylcarnitine translocase (CACT). These are essential molecules that play an
important role in the transport of activated long chain fatty acids from cytosol to the mitochondrial matrix where these subsequently
undergo beta-oxidation. It has been well established that fatty acid metabolism is vital for follicles and oocyte growth. This review
highlights the possible role of mitochondrial fatty transport acid system in ovarian function.
Keywords: Oocytes, Carnitine, Mitochondria, Fatty acids
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Introduction
acyl-carnitine by CPTI present in inner mitochondrial
membrane (figure 1). Acyl-carnitine is transferred to matrix via
CACT. After traversing membrane, acyl group is transferred by
CPT2 from carnitine to CoA which then undergoes citric acid
cycle. Carnitine is then shuttled back across membrane by
CACT and the process is repeated (7). TMLHE (epsilon-
trimethyllysine hydroxylase) is the gene encoding the first
enzyme-trimethyl lysine dioxygenase/hydroxylase, catalyzing
the rate limiting step of carnitine biosynthesis. Trimethyllysine
Mitochondrial function is essential for various cellular
activities including cell division and cell death or apoptosis (1).
Mitochondrial role has also been proven in human fertility (2).
Fertility is a key component of reproductive health in men and
women. Infertility has become a global health issue. Prevalence
of infertility in female is estimated to be 15% in India (3).
Ovarian function is integral to female fertility. Ovarian
folliculogenesis needs energy from various sources like
glucose, lipids and amino acids. Maximum energy is derived
from mitochondrial fatty acids oxidation (4). Role of
mitochondrial fatty acid β-oxidation is important in acquisition
of oocyte developmental competence.
dioxygenase /hydroxylase is
a non-heme ferrous iron
hydroxylase and 2-oxoglutarate dependent. It is the only
enzyme of carnitine biosynthesis located in the mitochondria
whereas the other three are cytosolic. The encoded protein
converts trimethyllysine (TML) into hydroxytrimethyllysine
Mitochondrial Fatty Acid Transport System
Mitochondrial fatty acid transport system includes
molecules such as 3-hydroxy-4-trimethylamino butyrate or
carnitine, organic cation transporter novel 2 (OCTN2),
carnitine palmitoyl transferase (CPT1), CPT2, and carnitine-
acylcarnitine translocase (CACT). The molecules play an
important role in the transport of activated long chain fatty acids
from cytosol to the mitochondrial matrix where these
subsequently undergo beta-oxidation. Fatty acid transporter or
carnitine plays an essential role in the transport of activated
fatty acids across the inner mitochondrial membrane (5).
Carnitine is 3-hydroxy-4-trimethylaminobutyrate and exists in
L and D isomers. Normal serum L-carnitine levels are between
(
HTML) Further,
trimethylaminobutaraldehyde dehydrogenase converts HTML
into trimethylamino- butaraldehyde (TAB).
in
mitochondria.
Hydroxytrimethyllysine aldolase converts TAB into
trimethylaminobutyrate/butyrobetaine which is catalyzed by Ƴ-
butyrobetaine dioxygenase and finally converted into carnitine
(
7).
Relevance to Ovarian Function
Successful reproduction depends on competent oocyte
capable of undergoing fertilization. Role of carnitine through
fatty acid metabolism has also been established in oocyte growth
and development. The antiapoptotic property of l-carnitine is to
stabilize mitochondrial membrane thereby increasing supply of
energy. Oocyte meiotic maturation needs energy from various
sources like glucose, lipids and amino acids. Oocyte maturation
includes cytoplasmic and nuclear events all of which are energy
consuming and require adequate ATP (8). Oxidative stress is one
of the mediators that affect quantity and quality of oocytes by
inducing apoptosis. Antioxidant supplementation has been
proved to protect oocytes against reactive oxygen species (ROS)
and oxidative stress.
2
5-50µM. Carnitine is synthesized from lysine and methionine
mainly in kidney, liver and brain (6). Free carnitine was first
isolated from bovine muscle and only L- isomer was found to
be bioactive. L-carnitine is also involved in maintaining
balance by removing accumulated toxic fatty acyl-CoA
metabolites. Carnitine is reabsorbed in circulation by renal
tubular active transport by OCTN2 transporter protein
regulated by SLC22A5 gene. OCTN2 is essential for carnitine
homeostasis. The fatty acids are first conjugated to form acyl
CoA. This acyl group is then transferred to carnitine forming
Corresponding author: Mona Sharma, Assistant Professor, Department of Reproductive Biology, All India Institute of Medical
Sciences, New Delhi-110029, India. Contact No. 9968147821. Email address:dr.mona18sharma@gmail.com
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